RESUMEN
BACKGROUND: COVID-19 counts 46 million people infected and killed more than 1.2 million. Hypoxaemia is one of the main clinical manifestations, especially in severe cases. HIF1α is a master transcription factor involved in the cellular response to oxygen levels. The immunopathogenesis of this severe form of COVID-19 is poorly understood. METHODS: We performed scRNAseq from leukocytes from five critically ill COVID-19 patients and characterized the expression of hypoxia-inducible factor1α and its transcriptionally regulated genes. Also performed metanalysis from the publicly available RNAseq data from COVID-19 bronchoalveolar cells. RESULTS: Critically-ill COVID-19 patients show a shift towards an immature myeloid profile in peripheral blood cells, including band neutrophils, immature monocytes, metamyelocytes, monocyte-macrophages, monocytoid precursors, and promyelocytes-myelocytes, together with mature monocytes and segmented neutrophils. May be the result of a physiological response known as emergency myelopoiesis. These cellular subsets and bronchoalveolar cells express HIF1α and their transcriptional targets related to inflammation (CXCL8, CXCR1, CXCR2, and CXCR4); virus sensing, (TLR2 and TLR4); and metabolism (SLC2A3, PFKFB3, PGK1, GAPDH and SOD2). CONCLUSIONS: The up-regulation and participation of HIF1α in events such as inflammation, immunometabolism, and TLR make it a potential molecular marker for COVID-19 severity and, interestingly, could represent a potential target for molecular therapy. Key messages Critically ill COVID-19 patients show emergency myelopoiesis. HIF1α and its transcriptionally regulated genes are expressed in immature myeloid cells which could serve as molecular targets. HIF1α and its transcriptionally regulated genes is also expressed in lung cells from critically ill COVID-19 patients which may partially explain the hypoxia related events.
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COVID-19/genética , Enfermedad Crítica , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Células Mieloides/metabolismo , Análisis de Secuencia de ARN/métodos , Femenino , Humanos , Masculino , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Regulación hacia ArribaRESUMEN
Interleukin- (IL-) 17 is increased in acute myocardial infarction (AMI) and plays a key role in inflammatory diseases through its involvement in the activation of leukocytes. Here, we describe for the first time the effect of IL-17 in the migration and activation of monocyte subsets in patients during ST-segment elevation myocardial infarction (STEMI) and post-STEMI. We analyzed the circulating levels of IL-17 in patient plasma. A gradual increase in IL-17 was found in STEMI and post-STEMI patients. Additionally, IL-17 had a powerful effect on the recruitment of CD14++CD16+/CD14+CD16++ monocytes derived from patients post-STEMI compared with the monocytes from patients with STEMI, suggesting that IL-17 recruits monocytes with inflammatory activity post-STEMI. Furthermore, IL-17 increased the expression of TLR4 on CD14 + CD16 - and CD14++CD16+/CD14+CD16++ monocytes post-STEMI and might enhance the response to danger-associated molecular patterns post-STEMI. Moreover, IL-17 induced secretion of IL-6 from CD14++CD16- and CD14++CD16+/CD14+CD16++ monocytes both in STEMI and in post-STEMI, which indicates that IL-17 has an effect on the secretion of proinflammatory cytokines from monocytes during STEMI and post-STEMI. Overall, we demonstrate that in STEMI and post-STEMI, IL-17 is increased and induces the migration and activation of monocyte subsets, possibly contributing to the inflammatory response through TLR4 and IL-6 secretion.
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Endotelio Vascular/metabolismo , Interleucina-17/metabolismo , Monocitos/inmunología , Infarto del Miocardio/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Electrocardiografía , Endotelio Vascular/patología , Femenino , Células Endoteliales de la Vena Umbilical Humana , Humanos , Interleucina-6/metabolismo , Receptores de Lipopolisacáridos/metabolismo , Masculino , Persona de Mediana Edad , Receptores de IgG/metabolismo , Receptor Toll-Like 4/metabolismoRESUMEN
BACKGROUND: Cytokines and macrophages play a central role in the development of atherosclerosis. Interleukin (IL)-17 is a pro-inflammatory cytokine with differential effects on innate immune cells. We investigated the effects of IL-17 on macrophage differentiation and foam cell formation and activation in response to oxidized low-density lipoprotein (oxLDL). METHODS: Human monocytes were treated with IL-17 to induce macrophage differentiation. As controls, human monocytes were differentiated into M1 macrophages (M1) or M2 macrophages (M2). Subsequently, we analyzed the expression levels of markers such as CD80, CD36 and Toll-like receptors (TLRs) as well as foam cell formation and cytokines in M1, M2 and macrophages differentiated with IL-17 with or without oxLDL. RESULTS: The expression of M1 or M2 markers or cytokines was not induced in macrophages differentiated with IL-17. Macrophages differentiated with IL-17 formed few foam cells, with an average proportion of 20%, and expressed 3 times as much TLR2 and 3.8 times as much TLR4 as M0 macrophages. Additionally, macrophages differentiated with IL-17 acquired inflammatory capacity in response to oxLDL through the expression of specific markers, such as CD80, which increased 18-times compared with macrophages differentiated with IL-17 alone, and secreted 1.3 times less tumor necrosis factor (TNF)-α than M1. Additionally, oxLDL increased the levels of CD80, CD86 and IL-6 by 5.7, 2.8 and 1.4 times in M1 compared with M1 in the absence of oxLDL. In M2, oxLDL induced increases in the secretion of IL-6 and TNF-α that were 1.9 times and 1.2 times smaller, respectively, than those observed in M1. CONCLUSION: Our study demonstrates that differentiation of macrophages with IL-17 does not induce the expression of markers or cytokines characteristic of M1 or M2 and these macrophages form few foam cells; however, the expression of TLR is increased. Moreover, these macrophages acquire the inflammatory capacity as evidenced by the expression of costimulatory molecules and secretion of pro-inflammatory cytokines in response to oxLDL. These findings suggest that the activation of macrophages differentiated with IL-17 by oxLDL contributes to the inflammatory process of atherosclerosis.
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Expresión Génica/efectos de los fármacos , Interleucina-17/farmacología , Interleucina-6/metabolismo , Lipoproteínas LDL/farmacología , Macrófagos/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismo , Antígeno B7-1/genética , Antígeno B7-1/inmunología , Antígeno B7-2/genética , Antígeno B7-2/inmunología , Diferenciación Celular , Humanos , Interleucina-6/genética , Interleucina-6/inmunología , Macrófagos/citología , Macrófagos/inmunología , Cultivo Primario de Células , Receptor Toll-Like 2/genética , Receptor Toll-Like 2/inmunología , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/inmunología , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
BACKGROUND: The anti-neutrophil cytoplasmic antibody-associated (ANCA) vasculitides includes granulomatosis with polyangiitis (Wegener's) (GPW), Chrug-Strauss syndrome (CSS) and microscopic polyangiitis (MPA). Since it has low incidence in our field, there are a few published papers. The aim of this study was to report the clinical characteristics, activity and damage of these vasculitides in Mexico City's metropolitan eastern area. METHODS: We studied 28 cases with ANCA-associated vasculitis in the aforementioned area. The classification was made according to the ACR 1990 criteria, the Chapel Hill 2012 consensus, and the EULAR 2007 recommendations. We collected demographic data, as well as data of clinical manifestations, laboratory, management and outcomes. The activity was established using the Birmingham Vasculitis Activity Score (BVAS) and the damage using the Vasculitis Damage Index (VDI). We used paired t test and 95% confidence intervals (95% CI). RESULTS: 15 females and 13 males were included, 20 with GPW and 8 with CCS. The mean age was 50.1 ± 12.7 years, and the evolution time was 69 ± 49.6 months. We didn't find cases of MAP. 23 patients (82.1%) had general symptoms. The initial and final BVAS means were 10.5 and 1.5 (p < 0.001) and the global VDI was 2.4. CONCLUSIONS: The presence of ANCA-associated vasculitides is rare in the eastern Metropolitan area of Mexico City. GPW was predominant over CCS, and MPA was absent. They are multi-system vasculitides with high scores of initial activity and moderate damage.
Introducción: las vasculitis asociadas a anticuerpos anticitoplasma de neutrófilo (ANCA) incluyen la granulomatosis con poliangeítis (GPW), el síndrome de Churg-Strauss (SChS) y la poliangeítis microscópica (PAM). Como son de baja incidencia, los informes son escasos. El objetivo fue reportar las características clínicas, la actividad y el daño de casos con estas vasculitis en la zona oriente de la Ciudad de México. Métodos: Se incluyeron 28 casos. La clasificación de las vasculitis se hizo según los criterios ACR 1990, Chapel Hill 2012 y EULAR 2007. Se recabaron datos demográficos, manifestaciones clínicas, de laboratorio, tratamientos y evolución clínica. Se determinó el puntaje de actividad de Birmingham (BVAS) y el daño de la vasculitis (VDI). Se utilizó la prueba t pareada e intervalos de confianza al 95% (IC 95%). Resultados: 15 mujeres y 13 hombres fueron incluidos, 20 con GPW y 8 con SChS, con edad de 50.1 ± 12.7 años y evolución de 69 ± 49.6 meses. No hubo casos con PAM. Presentaron ataque al estado general 23 (82.1%). Los promedios BVAS inicial y final fueron: 10.5 y 1.5 (p < 0.001) y el VDI global fue de 2.4. Conclusiones: las vasculitis asociadas a ANCA son raras en esta zona de la Ciudad de México. Predominaron los casos de GPW sobre SChS y fueron nulos para PAM. Tienen presentación multisistémica, altos puntajes de actividad inicial y daño moderado.
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Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/diagnóstico , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/epidemiología , Salud Urbana/estadística & datos numéricos , Adulto , Anciano , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/complicaciones , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/terapia , Femenino , Estudios de Seguimiento , Humanos , Masculino , México/epidemiología , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
BACKGROUND: Neonates undergoing surgery require analgesic medication to ameliorate acute pain. These medications produce negative side effects. Docosahexaenoic acid (DHA) has an antinociceptive effect in animals, but this has not been evaluated in human neonates. We evaluated the DHA effect on cumulative dose and duration of analgesics administered to neonates undergoing cardiovascular surgery. METHODS: A secondary analysis was performed with data from a clinical trial, in which enteral DHA was administered perioperatively compared with sunflower oil (SO). Present study assessed the antinociceptive effect of DHA by measuring the cumulative dose and duration of analgesics administered during postoperative stay in a neonatal intensive care unit. Multivariate linear regression models were performed. RESULTS: Seventeen neonates received DHA and 18 received SO in the control group. Compared with the control group, the DHA group received lower cumulative dose (14.6 ± 2.2 vs. 25.2 ± 4.8 µg/kg, p = 0.029) and shorter duration of buprenorphine (2 days (1-8) vs. 4.5 days (1-12); p = 0.053). After adjusting for confounders, the DHA group received significantly lesser buprenorphine (ß = -27 µg/kg, p = 0.028; R2 model = 0.90) for shorter duration (ß = -9 days, p = 0.003; R2 model = 0.94). No differences in fentanyl or ketorolac were detected. CONCLUSIONS: Buprenorphine administration was reduced in neonates who received DHA, suggesting that DHA likely has analgesic effects.
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Aorta/cirugía , Procedimiento de Blalock-Taussing/efectos adversos , Anomalías Cardiovasculares/cirugía , Suplementos Dietéticos , Ácidos Docosahexaenoicos/uso terapéutico , Fenómenos Fisiológicos Nutricionales del Lactante , Dolor Postoperatorio/prevención & control , Dolor Agudo/tratamiento farmacológico , Dolor Agudo/prevención & control , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/efectos adversos , Analgésicos Opioides/uso terapéutico , Antiinflamatorios no Esteroideos/efectos adversos , Antiinflamatorios no Esteroideos/uso terapéutico , Aorta/anomalías , Buprenorfina/administración & dosificación , Buprenorfina/efectos adversos , Buprenorfina/uso terapéutico , Suplementos Dietéticos/efectos adversos , Ácidos Docosahexaenoicos/efectos adversos , Método Doble Ciego , Femenino , Estudios de Seguimiento , Hospitales Pediátricos , Humanos , Recién Nacido , Unidades de Cuidado Intensivo Neonatal , Masculino , México , Dolor Postoperatorio/tratamiento farmacológico , Atención Perioperativa/efectos adversos , Factores de TiempoRESUMEN
BACKGROUND: Neonates undergoing surgery are at risk for uncontrolled inflammatory response and adverse clinical outcomes. Docosahexaenoic acid (DHA) ameliorates inflammation, improving clinical outcomes. However, its effect has not been evaluated in neonates undergoing surgery. We evaluated the effect of DHA on markers of inflammation and clinical outcomes in neonates undergoing surgery. METHODS: A double-blind clinical trial evaluated the effect of enteral DHA (DHA group) versus sunflower oil (SO group) perioperatively administered in neonates scheduled for cardiovascular surgery. Inflammation was evaluated by percentage of cells+ for cytokines and CD69 in mononuclear cells at baseline, 24 h and 7 days post surgery. Clinical outcomes measured were sepsis, organ dysfunctions (ODs), length of stay in intensive care and bleeding. Repeated measures analysis of variance and logistic regression were applied. RESULTS: Sixteen neonates received DHA and 18 received SO. Cells+ from neonates in the DHA group showed an early increase in receptor antagonist of interleukin (IL)-1+ (IL-1ra+) and IL-10+ and a late decrease in IL-6+. IL-1ß+ and IL-10+ changes were different between groups. After adjusting for confounders, less cells from DHA group were IL-1ß+, IL-6+, IL-1ra+ and IL-10+. DHA group presented less sepsis, ODs and shorter stay, but no difference in CD69+CD4+ cells or bleeding between groups. CONCLUSIONS: Administration of enteral DHA ameliorates markers of inflammation and improves clinical outcomes in surgical neonates.
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Anomalías Cardiovasculares/cirugía , Ácidos Docosahexaenoicos/uso terapéutico , Inflamación/prevención & control , Aceite de Girasol/uso terapéutico , Biomarcadores/sangre , Ácidos Docosahexaenoicos/administración & dosificación , Método Doble Ciego , Nutrición Enteral , Femenino , Humanos , Lactante , Fenómenos Fisiológicos Nutricionales del Lactante , Recién Nacido , Inflamación/sangre , Masculino , Periodo Perioperatorio , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/prevención & control , Aceite de Girasol/administración & dosificación , Resultado del TratamientoRESUMEN
Prolactin has an immunomodulatory effect and has been associated with B-cell-triggered autoimmune diseases, such as systemic lupus erythematosus (SLE). In mice that develop SLE, the PRL receptor is expressed in early bone marrow B-cells, and increased levels of PRL hasten disease manifestations, which are correlated with a reduction in the absolute number of immature B-cells. The aim of this work was to determine the effect of PRL in an in vitro system of B-cell tolerance using WEHI-231 cells and immature B-cells from lupus prone MRL/lpr mice. WEHI-231 cells express the long isoform of the PRL receptor, and PRL rescued the cells from cell death by decreasing the apoptosis induced by the cross-linking of the B-cell antigen receptor (BCR) as measured by Annexin V and active caspase-3. This decrease in apoptosis may have been due to the PRL and receptor interaction, which increased the relative expression of antiapoptotic Bcl-xL and decreased the relative expression of proapoptotic Bad. In immature B-cells from MRL/lpr mice, PRL increased the viability and decreased the apoptosis induced by the cross-linking of BCR, which may favor the maturation of self-reactive B-cells and contribute to the onset of disease.
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Apoptosis , Células Precursoras de Linfocitos B/citología , Células Precursoras de Linfocitos B/metabolismo , Prolactina/metabolismo , Receptores de Antígenos de Linfocitos B/metabolismo , Animales , Apoptosis/efectos de los fármacos , Apoptosis/genética , Apoptosis/inmunología , Caspasa 3/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/inmunología , Expresión Génica , Ratones , Ratones Endogámicos MRL lpr , Células Precursoras de Linfocitos B/efectos de los fármacos , Prolactina/farmacología , Unión Proteica , Receptores de Prolactina/genética , Receptores de Prolactina/metabolismoRESUMEN
UNLABELLED: Toll-like receptor (TLR)2, TLR4 and CD36 are central in inflammation and the development of atherosclerosis. Oxidized low-density lipoprotein (oxLDL) plays a critical role in this disease through its involvement in the formation of foam cells and the activation of leukocytes. The aim of this research was to analyze the role of TLR2, TLR4 and CD36 in foam cell differentiation and macrophage activation. METHODS: Human macrophages were incubated with monoclonal antibodies specific for TLR2, TLR4 and CD36 prior to stimulation with oxLDL. Subsequently, we analyzed foam cell formation, cytokine secretion, histocompatibility complex (MHC) class II molecules and CD86 expression and T cell proliferation. RESULTS: The stimulation of macrophages with oxLDL induced foam cell formation, cytokine secretion, HLA-DR and CD86 expression and T cell proliferation. The blockage of TLR2, TLR4 and CD36 reduced the secretion of IL-1ß, IL-6 and IL-8, the expression of HLA-DR and CD86, T cell proliferation and foam cell formation. However, the blockage of TLR2 did not affect the formation of foam cells. CONCLUSION: Our study demonstrates that TLR2, TLR4 and CD36 participate in the immune response to oxLDL by inducing an increase in pro-inflammatory cytokines, the expression HLA-DR and CD86 and the proliferation of T cells. However, TLR2 does not participate in the formation of foam cells, while TLR4 and CD36 play a relevant role in this process. These findings suggest that the activation of these receptors by oxLDL contributes to the pathogenesis of atherosclerosis.
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Antígenos CD36/metabolismo , Células Espumosas , Macrófagos/inmunología , Macrófagos/metabolismo , Receptor Toll-Like 2/metabolismo , Receptor Toll-Like 4/metabolismo , Adulto , Anticuerpos Monoclonales/farmacología , Antígeno B7-2/metabolismo , Antígenos CD36/antagonistas & inhibidores , Células Cultivadas , Citocinas/biosíntesis , Antígenos HLA-DR/inmunología , Antígenos HLA-DR/metabolismo , Voluntarios Sanos , Humanos , Lipoproteínas LDL/farmacología , Activación de Macrófagos/efectos de los fármacos , Activación de Macrófagos/inmunología , Macrófagos/efectos de los fármacos , Masculino , Subgrupos de Linfocitos T/efectos de los fármacos , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Receptor Toll-Like 2/antagonistas & inhibidores , Receptor Toll-Like 4/antagonistas & inhibidores , Adulto JovenRESUMEN
Atherosclerosis is a chronic inflammatory disease of the arterial wall characterized by innate and adaptive immune system involvement. A key component of atherosclerotic plaque inflammation is the persistence of different innate immune cell types including mast cells, neutrophils, natural killer cells, monocytes, macrophages and dendritic cells. Several endogenous signals such as oxidized low-density lipoproteins, and exogenous signals such as lipopolysaccharides, trigger the activation of these cells. In particular, these signals orchestrate the early and late inflammatory responses through the secretion of pro-inflammatory cytokines and contribute to plaque evolution through the formation of foam cells, among other events. In this review we discuss how innate immune system cells affect atherosclerosis pathogenesis.
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Aterosclerosis/inmunología , Inmunidad Innata , Animales , Aterosclerosis/metabolismo , Aterosclerosis/patología , Células Dendríticas/inmunología , Células Dendríticas/patología , Humanos , Inflamación/patología , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/patología , Macrófagos/inmunología , Macrófagos/patología , Mastocitos/inmunología , Mastocitos/patología , Monocitos/inmunología , Monocitos/patología , Neutrófilos/inmunología , Neutrófilos/patología , Placa Aterosclerótica/inmunología , Placa Aterosclerótica/patologíaRESUMEN
Monocyte locomotion inhibitory factor (MLIF) is a pentapeptide produced by Entamoeba histolytica that has a potent anti-inflammatory effect. Either MLIF or phosphate buffered saline (PBS) was administered directly onto the spinal cord (SC) immediately after injury. Motor recovery was evaluated. We also analyzed neuroprotection by quantifying the number of surviving ventral horn motor neurons and the persistence of rubrospinal tract neurons. To evaluate the mechanism through which MLIF improved the outcome of SC injury, we quantified the expression of inducible nitric oxide synthase (iNOS), interleukin-10 (IL-10), and transforming growth factor- ß (TGF- ß ) genes at the site of injury. Finally, the levels of nitric oxide and of lipid peroxidation were also determined in peripheral blood. Results showed that MLIF improved the rate of motor recovery and this correlated with an increased survival of ventral horn and rubrospinal neurons. These beneficial effects were in turn associated with a reduction in iNOS gene products and a significant upregulation of IL-10 and TGF- ß expression. In the same way, MLIF reduced the concentration of nitric oxide and the levels of lipid peroxidation in systemic circulation. The present results demonstrate for the first time the neuroprotective effects endowed by MLIF after SC injury.
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Entamoeba histolytica/química , Locomoción/efectos de los fármacos , Oligopéptidos/administración & dosificación , Traumatismos de la Médula Espinal/tratamiento farmacológico , Animales , Células del Asta Anterior/efectos de los fármacos , Células del Asta Anterior/fisiopatología , Humanos , Interleucina-10/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Fármacos Neuroprotectores/administración & dosificación , Óxido Nítrico Sintasa de Tipo II/metabolismo , Oligopéptidos/química , Ratas , Médula Espinal/efectos de los fármacos , Médula Espinal/fisiopatología , Traumatismos de la Médula Espinal/patología , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
Prolactin (PRL) plays an important role in modulating the immune response. In B cells, PRL enhances antibody production, including antibodies with self-specificity. In this study, our aims were to determine the level of PRL receptor expression during bone-marrow B-cell development and to assess whether the presence of high PRL serum concentrations influences absolute numbers of developing populations and disease outcome in lupus-prone murine models. We observed that the PRL-receptor is expressed in early bone-marrow B-cell; the expression in lupus-prone mice, which had the highest level of expression in pro-B cells and immature cells, differed from that in wild-type mice. These expression levels did not significantly change in response to hyperprolactinemia; however, populations of pro-B and immature cells from lupus-prone strains showed a decrease in the absolute numbers of cells with high PRL-receptor expression in response to PRL. Because immature self-reactive B cells are constantly being eliminated, we assessed the expression of survival factor BIRC5, which is more highly expressed in both pro-B and immature B-cells in response to PRL and correlates with the onset of disease. These results identify an important role of PRL in the early stages of the B-cell maturation process: PRL may promote the survival of self-reactive clones.
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Linfocitos B/inmunología , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/metabolismo , Prolactina/metabolismo , Animales , Anticuerpos Antinucleares/inmunología , Linfocitos B/metabolismo , Modelos Animales de Enfermedad , Femenino , Hiperprolactinemia/genética , Hiperprolactinemia/inmunología , Hiperprolactinemia/metabolismo , Inmunofenotipificación , Proteínas Inhibidoras de la Apoptosis/genética , Proteínas Inhibidoras de la Apoptosis/metabolismo , Lupus Eritematoso Sistémico/genética , Recuento de Linfocitos , Ratones , Ratones Endogámicos MRL lpr , Prolactina/sangre , Receptores de Prolactina/metabolismo , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , SurvivinRESUMEN
Existen evidencias de la relación entre el sistema inmune y el endocrino vía múltiples factores de comunicación, como citocinas, neuropéptidos, neurotransmisores y hormonas. Se ha demostrado la participación de la hormona prolactina en la respuesta inmune innata y adaptativa. Además de ser producida por la glándula pituitaria, también es producida y secretada por las células del sistema inmunológico. El objetivo de esta revisión fue puntualizar acerca de la participación de la prolactina secretada por estas células en la respuesta inmune.
Evidence exists about the relationship between the immune and the endocrine systems through communication of multiple factors such as cytokines, neuropeptides, neurotransmitters and hormones. Among the hormones, prolactin (PRL) has been shown to participate in the innate and adaptive immune response. In addition to being produced by the pituitary gland, PRL is also produced and secreted by cells of the immune system. The aim of this review is to update information about the involvement of PRL secreted by immune system cells in the immune response.
RESUMEN
BACKGROUND: Prolactin is secreted from the pituitary gland and other organs, as well as by cells such as lymphocytes. Prolactin has an immunostimulatory effect and is associated with autoimmune diseases that are characterised by abnormal B cell activation, such as systemic lupus erythematosus (SLE). Our aim was to determine if different splenic B cell subsets express the prolactin receptor and if the presence of prolactin influences these B cell subsets and correlates with development of lupus. RESULTS: Using real-time PCR and flow cytometry, we found that different subsets of immature (transitional) and mature (follicular, marginal zone) B cells express different levels of the prolactin receptor and are differentially affected by hyperprolactinaemia. We found that transitional B cells express the prolactin receptor at higher levels compared to mature B cells in C57BL/6 mice and the lupus-prone MRL/lpr and MRL mouse strains. Transitional-1 (T1) B cells showed a higher level of prolactin receptor expression in both MRL/lpr and MRL mice compared to C57BL/6 mice. Hyperprolactinaemia was induced using metoclopramide, which resulted in the development of early symptoms of SLE. We found that T1 B cells are the main targets of prolactin and that prolactin augments the absolute number of T1 B cells, which reflects the finding that this B cell subpopulation expresses the highest level of the prolactin receptor. CONCLUSIONS: We found that all B cell subsets express the prolactin receptor but that transitional B cells showed the highest prolactin receptor expression levels. Hyperprolactinaemia in mice susceptible to lupus accelerated the disease and increased the absolute numbers of T1 and T3 B cells but not of mature B cells, suggesting a primary effect of prolactin on the early stages of B cell maturation in the spleen and a role of prolactin in B cell differentiation, contributing to SLE onset.
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Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/metabolismo , Células Precursoras de Linfocitos B/metabolismo , Receptores de Prolactina/metabolismo , Animales , Subgrupos de Linfocitos B/metabolismo , Femenino , Expresión Génica , Centro Germinal/metabolismo , Hiperprolactinemia/inmunología , Hiperprolactinemia/metabolismo , Lupus Eritematoso Sistémico/genética , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos MRL lpr , Prolactina/administración & dosificación , Receptores de Prolactina/genética , Bazo/citología , Bazo/metabolismoRESUMEN
BACKGROUND AND AIMS: DNA vaccination has a great potential to decrease infectious diseases worldwide, such as rabies. Here we showed the effects of a single anti-rabies DNA vaccination applied intranasally (IN) on plasmid survival time, neutralizing antibody (NA) titers, G-protein expression and Th1/Th2-related cytokines. METHODS: Only one 50-µg dose of an anti-rabies DNA vaccine was IN administered to 160 Balb/c mice. Twenty mice were used for the neutralizing antibody study, 35 for the proliferation assay, 35 for Th1/Th2-related cytokines, 35 for glycoprotein expression by immunocytochemistry, and 35 for pGQH detection and G-protein mRNA expression. RESULTS: Th1-type related cytokines from spleen cells (IFN-γ, TNF-α, and IL-2) were detected. Rabies NA titers were ≥0.6 IUs from day 30 onward in the IN DNA-vaccinated group. The plasmid was identified in brains and lungs from days 3-15. The mRNA transcript was amplified in brains and lungs from days 3-30, and G-protein expression was observed in spleens, brains and lungs on days 3, 8, and 15. In all cases, a gradual decrease was observed on days 30 and 45 and absent on day 60. CONCLUSIONS: We found that Th1-type related cytokines (IL-2, IFN-γ, and TNF-α) were stimulated during the first month after DNA vaccination, correlating with the proliferation assays. Also, it was associated with the plasmid survival time remaining in lungs and brains prior to its degradation.
Asunto(s)
Citocinas/biosíntesis , Vacunas Antirrábicas/administración & dosificación , Células TH1/inmunología , Vacunas de ADN/administración & dosificación , Administración Intranasal , Animales , Anticuerpos Neutralizantes/biosíntesis , Inmunohistoquímica , Ratones , Ratones Endogámicos BALB C , Reacción en Cadena de la Polimerasa , Vacunas Antirrábicas/inmunología , Vacunas de ADN/inmunologíaRESUMEN
Prolactin (PRL) is a 23-kDa protein hormone that is synthesized mainly by the anterior pituitary gland. However, PRL can also be synthesized and secreted by extrapituitary tissues, particularly immune cells. A biallelic polymorphism (-1149 G/T) in the prolactin promoter has been shown to be functionally important, as modulation of prolactin expression has been associated with SLE in some populations. We have performed an association study using Mexican patients with SLE. We used qPCR to determine the SNP allele and genotype frequencies. We did not find statistically significant differences in allele and genotype frequencies between patients and healthy controls. However, we found a statistically significant association between the G allele and the presence of anti-dsDNA antibodies in serum (Allele frequency (G): P = 0.005; Genotyping frequency (GG): P = 0.001, OR = 7.8, 95% CI 3.59-27.1). Our data demonstrate that the prolactin promoter polymorphism -1149 G/T does not significantly contribute to SLE disease susceptibility but does predispose carriers to other immunological changes.
Asunto(s)
Anticuerpos Antinucleares/inmunología , Lupus Eritematoso Sistémico/genética , Lupus Eritematoso Sistémico/inmunología , Polimorfismo de Nucleótido Simple/genética , Prolactina/genética , Regiones Promotoras Genéticas/genética , Adulto , Anticuerpos Antinucleares/sangre , Femenino , Frecuencia de los Genes/genética , Genotipo , Humanos , Lupus Eritematoso Sistémico/diagnóstico , Masculino , México , Prolactina/sangre , Adulto JovenRESUMEN
Activation of CD4(+) T cells plays a main role in adaptive immune response by regulating cellular and humoral immunity via processes associated with changes in cell surface oligosaccharide receptors. Lectins are glycoproteins that specifically recognize oligosaccharides and have been used to characterize changes in oligosaccharides present on T cell surface and their effects on activation. A lectin from Amaranthus leucocarpus seeds (ALL) is specific for glycoprotein structures containing galactose-N-acetylgalactosamine and is able to bind to human and murine CD4(+) T cells, however, its effect on activation remains unclear. We examined the effect of ALL on the activation of peripheral blood human CD4(+) T cells and analyzed cell proliferation, expression of the activation-associated molecule CD25, secretion of the activation-dependent cytokine interleukin (IL)-2 and intracellular calcium influx changes using flow cytometry. CD4(+) T cells were stimulated with anti-CD3 antibodies that provided the first activation signal in the presence or absence of ALL. ALL alone did not induce CD4(+) T cell activation but when also stimulated with anti-CD3 antibodies, ALL up-regulated CD25 expression, cell proliferation, IL-2 secretion and an intracellular calcium influx in a dose-dependent manner. In addition, ALL recognized CD4(+) T cells expressing the CD69 and Ki67 molecules expressed only by activated T cells and induced production of the TH1-type cytokine interferon-gamma. Our findings indicate that ALL binds to human activated CD4(+) T cells and enhances the degree of activation of CD4(+) T cells that are stimulated with anti-CD3 antibodies. ALL provides a new tool for analyzing T cell activation mechanisms.
Asunto(s)
Anticuerpos/inmunología , Complejo CD3/inmunología , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/inmunología , Glicoproteínas/farmacología , Activación de Linfocitos/efectos de los fármacos , Activación de Linfocitos/inmunología , Lectinas de Plantas/farmacología , Anticuerpos/farmacología , Linfocitos T CD4-Positivos/citología , Calcio/metabolismo , Proliferación Celular/efectos de los fármacos , Humanos , Interferón gamma/biosíntesis , Interleucina-2/biosíntesis , Subunidad alfa del Receptor de Interleucina-2/metabolismo , Espacio Intracelular/efectos de los fármacos , Espacio Intracelular/metabolismo , Regulación hacia Arriba/efectos de los fármacosRESUMEN
BACKGROUND: Caprine arthritis encephalitis virus (CAEV) is a retrovirus belonging to the lentivirus genus that also includes the human immunodeficiency virus (HIV). CAEV may be transmitted to humans by goat milk consumption. It has been suggested that CAEV may also be involved in the immunological protection process against HIV, but this has not been demonstrated. Here we identified serological reactivity against CAEV gp135 in children who consumed goat milk. METHODS: Thirty sera samples from children (males between 6 and 16 years of age) who regularly consumed goat milk and a negative control of 30 serum samples from children (males between 6 and 12 years) with no previous contact with goats or goat dairy products were used. All sera were tested by Western blot against CAEV antigens. RESULTS: There were 18/30 serum samples from goat milk consumers that were reactive to CAEV gp135, and one reacted against gp50 simultaneously; none of the 30 serum samples from nonconsumers of goat dairy products reacted to viral proteins. CONCLUSIONS: These results showed that the positive response to gp135 may be the result of a repetitive stimulation without viral replication or the result of CAEV replication in humans. CAEV gp135 is codified by the env gene located on the viral particle surface as well as gp50. Moreover, there are similarities between CAEV gp135 and HIV-1 gp120, so there is a possibility that CAEV replicates in humans and may participate in immunological cross-phenomena, but this should be further studied.
Asunto(s)
Anticuerpos Antivirales/sangre , Virus de la Artritis-Encefalitis Caprina/inmunología , Cabras/virología , Infecciones por Lentivirus/transmisión , Leche/virología , Proteínas del Envoltorio Viral/inmunología , Adolescente , Animales , Niño , Humanos , Infecciones por Lentivirus/sangre , Infecciones por Lentivirus/virología , MasculinoRESUMEN
Entamoeba histolytica produces Monocyte Locomotion Inhibitory Factor (MLIF), which may contribute to the delayed inflammation observed in amoebic hepatic abscesses. Leukocytes are affected through the modulation of cytokine expression and/or production. We evaluated the effects of MLIF on the activation and production of intracellular cytokines in human CD4+ T lymphocytes by flow cytometry. Cells were stimulated for 24 h with PMA, MLIF, or PMA+MLIF. Cellular activation was measured using anti-CD69. Th1/Th2 production was studied by the expression of intracellular cytokines and cytokine/chemokine receptors. MLIF increased CD69 and induced the over-expression of the IL-lss, IFN-gamma, IL-2, IL-4, and IL-10 intracellular cytokines; PMA+MLIF inhibited Th1 cytokine (IFN-gamma) and increased Th2 cytokines (IL-4 and IL-10). The co-expression of the cytokine and chemokine receptors IFN-gamma/CCR5 and IL-1ss/CCR5 was inhibited by PMA+MLIF and Th2 co-expression was increased. MLIF effects varied depending on the conditions. MLIF alone activated the Th1 and Th2 cytokines and cytokine/receptor expression; however, PMA+MLIF increased the expression of Th2 but inhibited it in Th1.
Asunto(s)
Citocinas/biosíntesis , Oligopéptidos/farmacología , Receptores CCR4/efectos de los fármacos , Receptores CCR5/efectos de los fármacos , Células TH1/efectos de los fármacos , Células Th2/efectos de los fármacos , Células Cultivadas , Entamoeba histolytica/inmunología , Femenino , Citometría de Flujo , Humanos , Masculino , Oligopéptidos/biosíntesis , Receptores CCR4/inmunología , Receptores CCR5/inmunología , Acetato de Tetradecanoilforbol/farmacología , Células TH1/inmunología , Células Th2/inmunologíaRESUMEN
The human trichinosis is a cosmopolitan rare zoonosis in Mexico. It presents clinically, with an infectious toxic pattern. Typical symptomatology includes: fever, diarrhea, facial edema and myalgias, which can resemble other illnesses like typhoid fever, angioneurotic edema, septicemia, rheumatic disease-like vasculitis and dermato-polymyositis. The treatment is based on the use of antiparasites. In this paper a trichinosis case is described in a woman, 29 years old who lives in the metropolitan area, with a clinical pattern that suggest polymyositis. The diagnosis was confirmed through a muscle biopsy. The treatment was albendazole and prednisone with successful results.
Asunto(s)
Polimiositis/diagnóstico , Triquinelosis/diagnóstico , Adulto , Diagnóstico Diferencial , Femenino , HumanosRESUMEN
Entamoeba histolytica produces Monocyte Locomotion Inhibitory Factor (MLIF), which may contribute to the delayed inflammation observed in amoebic hepatic abscesses. Leukocytes are affected through the modulation of cytokine expression and/or production. We evaluated the effects of MLIF on the activation and production of intracellular cytokines in human CD4+ T lymphocytes by flow cytometry. Cells were stimulated for 24 h with PMA, MLIF, or PMA+MLIF. Cellular activation was measured using anti-CD69. Th1/Th2 production was studied by the expression of intracellular cytokines and cytokine/chemokine receptors. MLIF increased CD69 and induced the over-expression of the IL-l©¬, IFN-¥ã, IL-2, IL-4, and IL-10 intracellular cytokines; PMA+MLIF inhibited Th1 cytokine (IFN-¥ã) and increased Th2 cytokines (IL-4 and IL-10). The co-expression of the cytokine and chemokine receptors IFN-¥ã/CCR5 and IL-1©¬/CCR5 was inhibited by PMA+MLIF and Th2 co-expression was increased. MLIF effects varied depending on the conditions. MLIF alone activated the Th1 and Th2 cytokines and cytokine/receptor expression; however, PMA+MLIF increased the expression of Th2 but inhibited it in Th1.