RESUMEN
BACKGROUND: There is increasing interest in elucidating the relationship between adenoid hypertrophy (AH) and allergic rhinitis (AR). However, the impact of aeroallergen sensitization patterns on children with AH and AR remains unclear. METHODS: Patients aged 2-8 years (recruited from January 2019 to December 2022) with nasal symptoms were assessed for allergies, adenoid size, and respiratory viral infection history. The serum total immunoglobulin E (IgE) and specific IgE levels were measured, and flexible nasal endoscopy was performed. The relationship between AH, aeroallergen sensitization patterns, and lymphocyte subpopulations in adenoid samples was analyzed using flow cytometry. RESULTS: In total, 5281 children were enrolled (56.5% with AR; and 48.6% with AH). AH was more prevalent in children with AR. Compared to nonsensitized individuals, those polysensitized to molds had a higher prevalence of AH (adjusted OR 1.61, 95% CI 1.32-1.96) and a greater occurrence of two or more respiratory viral infections, particularly in adenoidectomy patients. The percentages and corrected absolute counts of regulatory T (Treg) cells, activated Tregs, class-switched memory B cells (CSMBs), natural killer (NK) T cells, and NK cell subpopulations were reduced in the adenoid tissues of children with both AH and AR (AH-AR) compared to AH-nAR children. Polysensitization in AH-AR children correlated with lower CSMB percentages. CONCLUSION: Polysensitivity to molds is associated with an increased risk of AH in children with AR. Fewer B cells, NK cells, and Treg cells with an effector/memory phenotype were detected in the adenoids of AR children, and these lower percentages of immune cells, particularly CSMBs, were closely linked to aeroallergen sensitization models and respiratory viral infection.
Asunto(s)
Tonsila Faríngea , Hipertrofia , Inmunoglobulina E , Rinitis Alérgica , Humanos , Tonsila Faríngea/inmunología , Tonsila Faríngea/patología , Niño , Masculino , Femenino , Hipertrofia/inmunología , Preescolar , Rinitis Alérgica/inmunología , Rinitis Alérgica/epidemiología , Inmunoglobulina E/sangre , Fenotipo , Alérgenos/inmunología , Linfocitos T Reguladores/inmunología , Prevalencia , AdenoidectomíaRESUMEN
PURPOSE: Adenotonsillar hypertrophy (ATH) is a medical condition characterized by the enlargement or swelling of the tonsils. The role of allergy in ATH has not been persuasively evidenced. Therefore, we investigated the state of humoral immunity and the presence of specific immunoglobulin E (sIgE) in tissues and sera in children suffering from TH. METHODS: According to the skin prick test (SPT) result, 44 ATH children were divided into the atopic and non-atopic groups. The level of sIgE against 30 inhalants and food allergens in the sera and tissue homogenates was measured by a commercial allergy immunoblotting kit. In addition, we evaluated the following variables in both tonsillar tissue homogenates and serum: total IgE, IgA, IgM, IgG, and tissue eosinophil counts. RESULTS: Our results showed that 21 (47.7%) of patients with ATH were sensitized to at least one allergen in the adenotonsillar sample and/or sera. Only two patients were negative for sIgE in the atopic group, but in the non-atopic group, only one had positive sIgE results. In the atopic group, 19 (86.4%) patients had positive sIgE in tonsillar tissues, and 18 (81.8%) had sensitized serum. There were no statistical differences in the case of other antibodies except IgE levels between the two groups. The average eosinophilic count was significantly higher in atopic patients than in the non-atopic group. CONCLUSION: The results of this study support the role of allergy in the pathogenesis of ATH and confirmed local allergic inflammation in tonsillar tissue.
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Tonsila Faríngea , Alérgenos , Hipertrofia , Inmunoglobulina E , Tonsila Palatina , Pruebas Cutáneas , Humanos , Hipertrofia/inmunología , Tonsila Faríngea/inmunología , Tonsila Faríngea/patología , Masculino , Tonsila Palatina/inmunología , Tonsila Palatina/patología , Niño , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Femenino , Alérgenos/inmunología , Preescolar , Hipersensibilidad/inmunología , AdolescenteRESUMEN
Macrophages are one of the top players when considering immune cells involved with tissue homeostasis. Recently, increasing evidence has demonstrated that macrophages could also present two major subsets during tissue healing: proliferative macrophages (M1-like), which are responsible for increasing myogenic cell proliferation, and restorative macrophages (M2-like), which are involved in the end of the mature muscle myogenesis. The participation and characterization of these macrophage subsets are critical during myogenesis to understand the inflammatory role of macrophages during muscle recovery and to create supportive strategies that can improve mass muscle maintenance. Indeed, most of our knowledge about macrophage subsets comes from skeletal muscle damage protocols, and we still do not know how these subsets can contribute to skeletal muscle adaptation. Thus, this narrative review aims to collect and discuss studies demonstrating the involvement of different macrophage subsets during the skeletal muscle damage/regeneration process, showcasing an essential role of these macrophage subsets during muscle adaptation induced by acute and chronic exercise programs.
Asunto(s)
Proliferación Celular , Ejercicio Físico , Hipertrofia/metabolismo , Mediadores de Inflamación/metabolismo , Inflamación/metabolismo , Macrófagos/metabolismo , Músculo Esquelético/metabolismo , Regeneración , Crecimiento del Músculo Esquelético , Animales , Humanos , Hipertrofia/inmunología , Hipertrofia/patología , Hipertrofia/fisiopatología , Inflamación/inmunología , Inflamación/patología , Inflamación/fisiopatología , Macrófagos/inmunología , Músculo Esquelético/inmunología , Músculo Esquelético/patología , Músculo Esquelético/fisiopatología , Fenotipo , Transducción de SeñalRESUMEN
Immune responses at the boundary between the host and the world beyond are complex and mucosal tissue homeostasis relies on them. Obstructive sleep apnea (OSA) is a syndrome suffered by children with hypertrophied tonsils. We have previously demonstrated that these tonsils present a defective regulatory B cell (Breg) compartment. Here, we extend those findings by uncovering the crucial role of resident pro-inflammatory B and T cells in sustaining tonsillar hypertrophy and hyperplasia by producing TNFα and IL17, respectively, in ex vivo cultures. Additionally, we detected prominent levels of expression of CD1d by tonsillar stratified as well as reticular epithelium, which have not previously been reported. Furthermore, we evidenced the hypertrophy of germinal centers (GC) and the general hyperplasia of B lymphocytes within the tissue and the lumen of the crypts. Of note, such B cells resulted mainly (IgG/IgM)+ cells, with some IgA+ cells located marginally in the follicles. Finally, by combining bacterial culture from the tonsillar core and subsequent identification of the respective isolates, we determined the most prevalent species within the cohort of OSA patients. Although the isolated species are considered normal oropharyngeal commensals in children, we confirmed their capacity to breach the epithelial barrier. Our work sheds light on the pathological mechanism underlying OSA, highlighting the relevance taken by the host immune system when defining infection versus colonization, and opening alternatives of treatment.
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Bacterias/inmunología , Infecciones Bacterianas/inmunología , Mucosa Bucal/inmunología , Mucosa Bucal/microbiología , Apnea Obstructiva del Sueño/complicaciones , Apnea Obstructiva del Sueño/inmunología , Tonsilitis/complicaciones , Tonsilitis/inmunología , Adolescente , Linfocitos B/inmunología , Bacterias/aislamiento & purificación , Infecciones Bacterianas/microbiología , Células Cultivadas , Niño , Preescolar , Enfermedad Crónica , Estudios de Cohortes , Citocinas/metabolismo , Femenino , Centro Germinal/inmunología , Humanos , Hipertrofia/inmunología , Hipertrofia/metabolismo , Inflamación/inmunología , Inflamación/metabolismo , Masculino , Tonsila Palatina/inmunología , Linfocitos T/inmunología , Tonsilectomía , Tonsilitis/microbiología , Tonsilitis/cirugíaRESUMEN
RATIONALE: Idiopathic hypertrophic pachymeningitis (IHP) is a rare neurological disorder without a definite etiology. Diagnosis is mainly based on exclusion of other etiologies. PATIENT CONCERNS: A 41-year-old male patient presented with insidious onset headache of 3-month duration. DIAGNOSES: Contrast-enhanced brain magnetic resonance imaging (MRI) revealed diffuse pachymeningeal enhancement over bilateral cerebral hemispheres and the tentorium cerebelli. Lumbar puncture showed increased pressure, lymphocytic pleocytosis, and elevated protein level with normal glucose concentration. Blood tests detected elevated erythrocyte sedimentation rate (ESR) and C-reactive protein. Pathological examination of the dura mater from the right frontal convexity disclosed coarse collagenous deposition with focal lymphoid aggregation. After malignancy and infectious etiologies were excluded, a diagnosis of IHP was made. INTERVENTIONS: Oral prednisolone and azathioprine followed by methotrexate were administered. OUTCOMES: During the 7-year follow-up period, although the patient was not totally headache-free, medical therapy significantly reduced the severity of headache. Follow-up MRI studies showed a reduction in meningeal enhancement and serial ESR measurements revealed a trend of improvement. LESSONS: Methotrexate therapy may be considered in cases of steroid-resistant IHP. In addition to clinical evaluation, serial ESR testing may be considered to guide the treatment strategy and assess the response to therapy.
Asunto(s)
Anticuerpos Anticardiolipina/inmunología , Cefalea/inmunología , Hipertrofia/inmunología , Meningitis/inmunología , Adulto , Encéfalo/inmunología , Encéfalo/patología , Duramadre/inmunología , Duramadre/patología , Humanos , MasculinoRESUMEN
BACKGROUND: Dural thickening is observed in lymphoma, dural carcinomatosis, meningioma, tuberculosis, and autoimmune diseases. We encountered a patient with dural thickening and complaints of neck and back pain, numbness and loss of strength in the hands. The patient also suffered from polychondritis and had previously received steroid and methotrexate treatment for this indication. The patients' serum was also positive for ANA, yet she did not have any other findings suggesting lupus. Our radiological and pathological analysis revealed IHSP (IgG4-related hypertrophic sclerosing pachymeningitis). In this review study, we provided a detailed literature survey to increase the awareness about IHSP in the neurosurgical community. METHODS: MRI (magnetic resonance imaging)-based radiological analyses revealed a posterior extramedullary spinal mass extending from C2 to T2-T3 level. The dural mass was surgically excised and a broad panel of immunohistochemical markers including S100, EMA, CD246/ALK-1, CD45, CD20, CD79a, CD138, CD68, CD1a and CD34 was studied. Immunoglobulin heavy chain/kappa chain gene rearrangement analysis was performed which ruled out a lymphoproliferative disorder. RESULTS: MRI and pathological findings suggested IHSP. As the disease relapsed with a new anterior extramedullary multilobulated lesion extending from C5 to T1 level, the patient is now closely monitored for further medical and surgical treatment. CONCLUSIONS: IHSP is a relatively novel entity of hypertrophic pachymeningitis and should be included in the differential diagnosis of dural thickening. The fibrosis accompanying IHSP may not respond to medical treatment, which includes steroids and immunosuppressive agents. Additionally, neurological deficits, seizures, spinal decompression, hydrocephalus, or brainstem compression necessitate early surgical intervention. A continued vigilance is also necessary as the disease may relapse long-term following surgical treatment.
Asunto(s)
Hipertrofia/diagnóstico , Inmunoglobulina G/inmunología , Meningitis/diagnóstico , Recurrencia Local de Neoplasia/diagnóstico , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/inmunología , Diagnóstico Diferencial , Humanos , Hipertrofia/inmunología , Hipertrofia/cirugía , Meningitis/inmunología , Meningitis/cirugía , Recurrencia Local de Neoplasia/inmunología , Recurrencia Local de Neoplasia/cirugíaRESUMEN
BACKGROUND: Tonsil hypertrophy has negative impact on children's health, but its pathogenesis remains obscure despite the fact that numerous bacteriological studies have been carried out. Understanding the innate immune and inflammatory states of hypertrophic tonsils with different clinical manifestations is of great significance for defining the pathogenesis of tonsil hypertrophy and establishing treatment strategies. The present study was undertaken to examine the characteristics of innate immunity and inflammation in children with hypertrophic palatine tonsils and different clinical manifestations. METHODS: Tonsil tissues were surgically removed from the patients and classified based on the patients' clinical manifestations. The patients were divided into three groups: 1) Control group; 2) Tonsil Hypertrophy (TH) group; and 3) Tonsil Hypertrophy combined with Recurrent Infection (TH + RI) group. The immune and inflammatory statuses of these tissues were characterized using qRT-PCR and ELISA methods. RESULTS: Viral protein 1 (VP1) was highly expressed in TH group, but not in TH + RI group. In TH group, elevated expression was observed in the innate immune mediators, including retinoic acid-inducible gene I (RIG-I), interferon alpha (IFN-α), mitochondrial antiviral-signaling protein (MAVS), NLR family pyrin domain containing 3 (NLRP3), toll-like receptor (TLR) 4 and TLR7. Consistent with the innate immune profile, the expression of inflammatory markers (IL-1ß, NF-κB and IL-7) was also significantly elevated in TH group. Meanwhile, the COX-2/PGE2/EP4 signaling pathway was found to be involved in the inflammatory response and the formation of fibroblasts. CONCLUSIONS: Innate immune and inflammatory responses are more active in simple hypertrophic tonsils, rather than hypertrophic tonsils with recurrent inflammation. A local relative immune deficiency in the hypertrophic tonsils may be a causative factor for recurrent tonsillitis in TH + RI. These differences, together with the patient's clinical manifestations, suggest that tonsillar hypertrophy might be regulated by diverse immune and/or inflammatory mechanism through which novel therapeutic strategies might be created.
Asunto(s)
Inmunidad Innata , Inflamación , Tonsila Palatina/patología , Niño , Ensayo de Inmunoadsorción Enzimática , Humanos , Hipertrofia/inmunología , Interferón-alfa/genética , Interferón-alfa/metabolismo , Tonsila Palatina/inmunología , Tonsila Palatina/cirugía , ARN/análisis , Reacción en Cadena en Tiempo Real de la Polimerasa , Recurrencia , Tonsilectomía , Proteínas Virales/genética , Proteínas Virales/metabolismo , Virosis/inmunologíaRESUMEN
The exact mechanisms of Adenoid hypertrophy (AHT) pathogenesis and otitis media with effusion (OME) are unclear but there is increasing evidence that allergies may play a role. We aimed to investigate the prevalence of atopy and the effect of anti-allergic drugs in patients with AHT and OME. In a non-randomized, prospective cross-sectional study, 122 patients younger than 18 years of age with AHT or OME were included. Atopic patients based on clinical symptoms of allergic disorders and/or elevated levels of total serum immunoglobulin E (IgE) were referred to allergists and tested for allergen sensitization by skin prick test (SPT). Atopic patients were treated with nasal corticosteroids and antihistamines. Response to treatment was evaluated by comparing symptoms score before and after the treatment. In this study 122 patients were evaluated, 116 of them had AHT and 30 patients had OME. The mean age of participants was 6.7±2.4 years old and 68 of them (55.7%) were male. Allergic symptoms were observed in 38 patients with AHT (32.7%) and nine patients with OME (30%). Among the total cases, 34 patients (28%) were considered atopic. SPT was performed on 25 (73%) cases of atopic patients, with 11 (44 %) positive results. The mean symptom score of AHT and OME decreased significantly after treatment respectively, (p=0.001, p=0.007). According to this study, atopy was relatively common in patients with AHT and OME. Treatment with nasal corticosteroid and antihistamines were effective in these patients.
Asunto(s)
Tonsila Faríngea/inmunología , Hipersensibilidad/inmunología , Hipertrofia/inmunología , Otitis Media con Derrame/inmunología , Otitis Media/inmunología , Niño , Estudios Transversales , Femenino , Humanos , Hipersensibilidad Inmediata/inmunología , Inmunoglobulina E/inmunología , Masculino , Prevalencia , Estudios Prospectivos , Pruebas Cutáneas/métodosRESUMEN
Osteoarthritis (OA) is generally considered to be characterized by progressive articular cartilage destruction. Increasing evidence demonstrates that CDK9, which is a member of cyclin-dependent kinase family, plays a significant role in the regulation of acute and chronic inflammatory diseases. IL-1ß, a major proinflammatory cytokine, was used to establish a model of OA in vitro after stimulating chondrocytes. We found that CDK9 was highly expressed in in vitro and in vivo models of inflammation. The role of LDC000067 (abbreviated as LDC067), a specific inhibitor of CDK9, in protecting articular cartilage from immune response has not been fully clarified. Intriguingly, in this study, we demonstrated that LDC067 prevented IL-1ß-induced production of metalloproteinases (MMPs) and inflammatory cytokines, including MMP3, MMP9, MMP13, IL-6, IL-8 and TNF-É. Furthermore, we revealed that LDC067 inhibited IL-1ß-induced NF-κB signaling pathway activation in chondrocytes. The inhibition of CDK9 could also delay cartilage degeneration in an anterior cruciate ligament transection (ACLT) mouse model in vivo. Taken together, these results highlighted the significance of this CDK9 inhibitor in preventing cartilage destruction and indicated that LDC067 might serve as a potential therapeutic agent for OA.
Asunto(s)
Condrocitos/inmunología , Quinasa 9 Dependiente de la Ciclina/inmunología , Inflamación/inmunología , Osteoartritis/inmunología , Animales , Línea Celular , Condrocitos/efectos de los fármacos , Condrocitos/patología , Quinasa 9 Dependiente de la Ciclina/análisis , Quinasa 9 Dependiente de la Ciclina/antagonistas & inhibidores , Hipertrofia/tratamiento farmacológico , Hipertrofia/inmunología , Hipertrofia/patología , Inflamación/tratamiento farmacológico , Inflamación/patología , Interleucina-1beta/análisis , Interleucina-1beta/inmunología , Masculino , Metaloproteinasas de la Matriz/análisis , Metaloproteinasas de la Matriz/inmunología , Ratones Endogámicos C57BL , FN-kappa B/análisis , FN-kappa B/inmunología , Osteoartritis/tratamiento farmacológico , Osteoartritis/patología , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirimidinas/uso terapéutico , Sulfonamidas/uso terapéutico , Factor de Necrosis Tumoral alfa/análisis , Factor de Necrosis Tumoral alfa/inmunologíaAsunto(s)
Dermatosis del Cuero Cabelludo/patología , Cuero Cabelludo/patología , Adulto , Humanos , Hipertrofia/diagnóstico por imagen , Hipertrofia/inmunología , Hipertrofia/patología , Deficiencia de IgA/diagnóstico , Masculino , Cuero Cabelludo/diagnóstico por imagen , Cuero Cabelludo/inmunología , Dermatosis del Cuero Cabelludo/diagnóstico por imagen , Dermatosis del Cuero Cabelludo/inmunologíaRESUMEN
Recent studies have suggested that maternal high-fat (HF) diet caused inflammation changes in adipose tissue; however, it remains unclear if maternal diet intervention before pregnancy rescues such effects in offspring. To address this question, female mice were continued on a normal-fat (NF group), or a HF diet (HF group) or transitioned from a HF diet to a NF diet at 1 (H1N group), 5 (H5N group) or 9 weeks (H9N group) prior to pregnancy. Among the three intervention groups, the H9N offspring displayed less and steady body weight gain, and maintained glucose tolerance, whereas the H1N and H5N offspring showed exacerbate these phenotypes. The H1N and H5N, but not the H9N offspring, displayed adipocyte hypertrophy associated with increased expression of genes involved in fat deposition. The H1N and H5N, but not the H9N adipose tissue, displayed increased macrophage infiltration with enhanced expression of inflammatory cytokine genes. In addition, overactivation of the NF-κB and the JNK signaling were observed in the H1N adipose tissue. Overall, our study showed that a long-term but not a short- or medium-term diet intervention before pregnancy released offspring adipose tissue inflammation induced by maternal HF diet, which adds details in our understanding how the maternal environment either promotes or discourages onset of disease in offspring. Clinically, this study is of great value for providing evidence in the design of clinical trials to evaluate the urgently required intervention strategies to minimize the intergenerational cycle of obesity.
Asunto(s)
Tejido Adiposo/inmunología , Dieta Saludable , Dieta Alta en Grasa/efectos adversos , Inflamación/prevención & control , Fenómenos Fisiologicos Nutricionales Maternos , Adipocitos/inmunología , Adipocitos/patología , Animales , Grasas de la Dieta/efectos adversos , Femenino , Regulación de la Expresión Génica/inmunología , Hipertrofia/inmunología , Hipertrofia/patología , Inflamación/metabolismo , Inflamación/patología , Sistema de Señalización de MAP Quinasas/inmunología , Macrófagos/inmunología , Macrófagos/patología , Masculino , Fenómenos Fisiologicos Nutricionales Maternos/inmunología , Ratones de la Cepa 129 , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , Embarazo , Efectos Tardíos de la Exposición Prenatal/inmunología , Efectos Tardíos de la Exposición Prenatal/patología , Factores de TiempoRESUMEN
Exposure to tobacco smoke is associated with a higher risk of respiratory tract diseases. The aim of this study was to determine the influence of passive smoking on selected characteristics of children with adenoid hypertrophy. Sixty-one children with adenoid hypertrophy were enrolled in the prospective study. Differences in bacterial colonisation of middle nasal meatus and nasopharynx and changes in selected laboratory immune and inflammatory markers according to the tobacco smoke exposure were analysed. Exposure to tobacco smoke was associated with significantly higher colonisation of pathogenic bacteria and polymicrobial growth of pathogenic bacteria (≥ 2 bacteria) in middle nasal meatus compared to non-exposed children (P = 0.045, P = 0.032, respectively). Identification of pathogenic bacteria in the middle nasal meatus did not correlate with isolation of pathogenic bacteria in the nasopharynx in either group of children. Parameters of humoral immunity in serum, IgA and IgG, were detected at higher concentrations in children exposed to tobacco smoke (P = 0.047, P = 0.031, respectively). Differences in selected parameters of cellular immunity in peripheral blood according to passive smoking were not observed. Tobacco smoke exposure is related to increased colonisation by pathogenic bacteria in middle nasal meatus and elevation of IgA and IgG in peripheral blood, but does not seem to influence markers of cellular immunity parameters in children with adenoid hypertrophy. Avoidance of passive smoking could be recommended as a universal preventive strategy against microbial colonisation of the upper airways and development of various inflammatory diseases in children, e.g. adenoid hypertrophy.
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Bacterias/aislamiento & purificación , Microbiota , Cavidad Nasal/microbiología , Nasofaringe/microbiología , Contaminación por Humo de Tabaco , Tonsila Faríngea/inmunología , Tonsila Faríngea/microbiología , Tonsila Faríngea/patología , Adolescente , Niño , Preescolar , Femenino , Humanos , Hipertrofia/inmunología , Hipertrofia/microbiología , Masculino , Estudios ProspectivosRESUMEN
Cartilage lesions in degenerative osteoarthritis (OA) are involved with pathological microenvironmental alterations induced by inflammatory macrophages, and apoptotic and/or hypertrophic chondrocytes. However, current non-operative therapies for cartilage repair in OA can rarely achieve long-term and satisfactory outcomes. This study aims to evaluate a newly developed squid type II collagen (SCII) for repairing OA-induced cartilage lesions. Our in vitro data show that SCII induces M2 polarization of macrophages, and activates macrophages to express pro-chondrogenic genes (TGF-ß and IGF), which greatly improves the microenvironment around chondrocytes to produce type II collagen and glycosaminoglycan. In addition, glycine in SCII activates glycine receptors on inflammatory chondrocytes to decrease intracellular calcium concentration, leading to effective inhibition of chondrocyte apoptosis and hypertrophy. The in vitro effects of SCII are further confirmed in vivo. In a rat model of OA, SCII increases the ratio of M2 macrophages, elevates the levels of pro-chondrogenic cytokines (TGF-ß1 and TGF-ß3) in synovial fluid, and inhibits chondrocyte apoptosis and MMP13 production. Our findings show that SCII immunomodulates M2 activation of macrophages to skew the local OA microenvironment towards a pro-chondrogenic atmosphere, and promotes cartilage repair under inflammatory condition. It shows great potential for SCII to be a novel biomaterial for cartilage repair in OA.
Asunto(s)
Colágeno Tipo II/metabolismo , Macrófagos/metabolismo , Osteoartritis/inmunología , Osteoartritis/metabolismo , Animales , Apoptosis/fisiología , Condrocitos/metabolismo , Glicosaminoglicanos/metabolismo , Humanos , Hipertrofia/inmunología , Hipertrofia/metabolismo , Macrófagos/inmunologíaRESUMEN
Interleukin-6 (IL-6) signaling is critical for cardiomyocyte hypertrophy, while the role of IL-6 in the pathogenesis of myocardium hypertrophy remains controversial. To determine the essential role of IL-6 signaling for the cardiac development during AngII-induced hypertension, and to elucidate the mechanisms, wild-type (WT) and IL-6 knockout (IL-6 KO) mice were infused subcutaneously with either vehicle or AngII (1.5 µg/h/mouse) for 1 week. Immunohistological and serum studies revealed that the extents of cardiac fibrosis, inflammation and apoptosis were reduced in IL-6 KO heart during AngII-stimulation, while cardiac hypertrophy was obviously induced. To investigate the underlying mechanisms, by using myocardial tissue and neonatal cardiomyocytes, we observed that IL-6/STAT3 signaling was activated under the stimulation of AngII both in vivo and in vitro. Further investigation suggested that STAT3 activation enhances the inhibitory effect of EndoG on MEF2A and hampers cardiomyocyte hypertrophy. Our study is the first to show the important role of IL-6 in regulating cardiac pathogenesis via inflammation and apoptosis during AngII-induced hypertension. We also provide a novel link between IL-6/STAT3 and EndoG/MEF2A pathway that affects cardiac hypertrophy during AngII stimulation.
Asunto(s)
Angiotensina II/administración & dosificación , Cardiomiopatías/inmunología , Cardiomiopatías/patología , Interleucina-6/inmunología , Miocitos Cardíacos/inmunología , Miocitos Cardíacos/patología , Factor de Transcripción STAT3/inmunología , Animales , Cardiomiopatías/inducido químicamente , Células Cultivadas , Hipertrofia/inmunología , Hipertrofia/patología , Interleucina-6/genética , Masculino , Ratones , Ratones Noqueados , Miocitos Cardíacos/efectos de los fármacosRESUMEN
Hypertrophy of the breast (macromastia and gigantomastia) is a rare medical condition of the breast connective tissues. The etiology of this condition is still not clear; rarely, gigantomastia has been reported to develop in the setting of an autoimmune illness. We reported a case of a 37-years-old woman with undifferentiated connective tissue disease of 2-years duration presented with enlargement of breasts. The breast enlargment started at 5 months of gestation. She successfully underwent reduction mammoplasty with free nipple graft. In the succeeding months the level of antinuclear ANA remained stable. It is uncertain whether a positive antinuclear antibodies in gigantomastia is a casuative agent or an effect.
Asunto(s)
Anticuerpos Antinucleares/sangre , Mama/anomalías , Hipertrofia/patología , Mamoplastia/métodos , Complicaciones del Embarazo/patología , Adulto , Mama/inmunología , Mama/patología , Mama/cirugía , Femenino , Humanos , Hipertrofia/inmunología , Hipertrofia/cirugía , Pezones/cirugía , Embarazo , Complicaciones del Embarazo/inmunología , Complicaciones del Embarazo/cirugíaRESUMEN
The molecular mechanism underlying the fibrosis of ligamentum flavum(LF) in patients with lumbar spinal canal stenosis(LSCS) remains unknown. MicroRNAs are reported to play important roles in regulating fibrosis in different organs. The present study aimed to identify fibrosis related miR-21 expression profile and investigate the pathological process of miR-21 in the fibrosis of LF hypertrophy and associated regulatory mechanisms. 15 patients with LSCS underwent surgical treatment were enrolled in this study. For the control group, 11 patients with lumbar disc herniation(LDH) was included. The LF thickness was measured on MRI. LF samples were obtained during the surgery. Fibrosis score was assessed by Masson's trichrome staining. The expression of miR-21 in LF tissues were determined by RT-PCR. Correlation among LF thickness, fibrosis score, and miR-21 expression was analyzed. In addition, Lentiviral vectors for miR-21 mimic were constructed and transfected into LF cells to examine the role of miR-21 in LF fibrosis. Types I and III collagen were used as indicators of fibrosis. IL-6 expression in LF cells after transfection was investigated by RT-PCR and ELISA. Patients in two groups showed similar outcomes regarding age, gender, level of LF tissue. The thickness and fibrosis score of LF in the LSCS group were significantly greater than those in LDH group (all P < 0.05). Similarly, the expression of miR-21 in LSCS group was substantially higher than that in LDH group(P < 0.05). Furthermore, the miR-21 expression exhibited positive correlations with the LF thickness (r = 0.595, P < 0.05) and fibrosis score (r = 0.608, P < 0.05). Of note, miR-21 over-expression increased the expression levels of collagen I and III (P < 0.05). Also, IL-6 expression and secretion in LF cells was elevated after transfection of miR-21 mimic. MiR-21 is a fibrosis-associated miRNA and promotes inflammation in LF tissue by activating IL-6 expression, leading to LF fibrosis and hypertrophy.
Asunto(s)
Regulación de la Expresión Génica , Inflamación/patología , Interleucina-6/genética , Ligamento Amarillo/patología , Vértebras Lumbares/patología , MicroARNs/genética , Estenosis Espinal/patología , Anciano , Células Cultivadas , Femenino , Fibrosis , Humanos , Hipertrofia/complicaciones , Hipertrofia/genética , Hipertrofia/inmunología , Hipertrofia/patología , Inflamación/complicaciones , Inflamación/genética , Inflamación/inmunología , Interleucina-6/inmunología , Ligamento Amarillo/inmunología , Vértebras Lumbares/inmunología , Masculino , MicroARNs/inmunología , Persona de Mediana Edad , Estudios Prospectivos , Estenosis Espinal/complicaciones , Estenosis Espinal/genética , Estenosis Espinal/inmunología , TranscriptomaRESUMEN
This study aimed to examine changes in the inflammatory response in early hypertrophic compared to normal wound healing. The immune system is thought to be involved in hypertrophic scar formation. However, the exact mechanism and time of onset of the derailment remain unknown. In a prospective observational study, skin biopsies were taken directly postwounding and 3 hours later from patients who had elective cardiothoracic surgery. The skin biopsies were analysed for mRNA, proteins and cells involved in the early inflammatory phase of wound healing. The endpoint was scar outcome (hypertrophic (HTS) or normal (NTS)) at one year after surgery. There were significant differences between the NTS and HTS groups regarding the fold changes of mRNA expression of P-selectin during surgery. Postoperative skin concentrations of inflammatory proteins IL-6, IL-8 and CCL2 were significantly lower in the HTS compared to the NTS group. Also, a trend of higher pre-operative M2 macrophage numbers was observed in the HTS group. Neutrophil numbers increased equally during surgery in both groups. The increase of P-selectin mRNA in hypertrophic wound healing could affect leucocyte migration. The decreased concentrations of inflammatory proteins in hypertrophic wound healing indicate a reduced inflammatory response, which has consequences for the treatment of hypertrophic scarring during the early inflammatory phase. In a conclusion, alterations of wound healing associated with hypertrophic scarring are visible as early as 3 hours postwounding and include a reduced rather than increased inflammatory protein response.
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Cicatriz/inmunología , Hipertrofia/inmunología , Cicatriz/metabolismo , Cicatriz/patología , Citocinas/metabolismo , Humanos , Infiltración Neutrófila , Estudios ProspectivosRESUMEN
Hypertrophic pachymeningitis secondary to IgG4-related disease is a rare but sometimes devastating cause of intracranial hypertension. It has the potential for an excellent response to corticosteroids or rituximab. We discuss the clinical presentation, imaging, histology (with its difficult distinction from lymphoma), management and follow-up of a case, including relapse and re-treatment following an initial response to rituximab.
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Hipertrofia/diagnóstico , Inmunoglobulina G , Hipertensión Intracraneal/diagnóstico , Adulto , Femenino , Humanos , Hipertrofia/inmunología , Hipertensión Intracraneal/inmunología , MeningitisRESUMEN
OBJECTIVE: This study aims to explore the role of the Th17 to Treg cell ratio in children with OSA and its relationship with allergic rhinitis. METHODS: The study included 127 children diagnosed with OSA by polysomnography (PSG) testing and 29 children without OSA. The 127 children with OSA were divided into the following groups: OSA with moderate adenoidal hypertrophy (n=47), OSA with severe adenoidal hypertrophy (n=49), and OSA complicated by allergic rhinitis (AR) (n=31). The adenoids of the 29 children without OSA were mildly hypertrophic. We measured the number of Th17 and Treg cells, the levels of related serum cytokines in cellular secretions, and the expression of key transcription factors in both the peripheral blood and adenoid tissue. The Th17/Treg ratio was calculated and analyzed between groups. The numbers of Th17 and Treg cells were measured by flow cytometry; the secreted IL-17, IL-10, and TGF-ß were measured by ELISA; and the expression levels of RORγt and Foxp3 were measured by RT-PCR. RESULTS: Compared with the control group, OSA children exhibited a significant increase in the number of peripheral Th17 cells, Th17-related cytokine secretion (IL-17), and RORγt mRNA levels, whereas they exhibited a decrease in the number of Treg cells, Treg-related cytokine secretions (IL-10, TGF-ß) and Foxp3 mRNA levels. The Th17/Treg ratio was higher (p<0.05) in the OSA groups than in the control group. The Th17/Treg ratio was correlated with the size of the adenoids. We also found that the Th17/Treg balance in OSA patients was complicated by allergic rhinitis; the increase was significantly larger in the AR group (p<0.05, p=0.021) than in OSA groups without AR. These results were observed in both the peripheral blood and local adenoid tissue. CONCLUSION: The Th17/Treg imbalance may increase the risk of developing OSA, and AR may promote the development of the disease. These results provide an alternative explanation for OSA pathogenesis that warrants additional research and presents new directions for the prevention and treatment of OSA in children.
Asunto(s)
Tonsila Faríngea/patología , ARN Mensajero/metabolismo , Rinitis Alérgica/inmunología , Apnea Obstructiva del Sueño/inmunología , Linfocitos T Reguladores , Células Th17 , Tonsila Faríngea/metabolismo , Niño , Preescolar , Femenino , Citometría de Flujo , Factores de Transcripción Forkhead/genética , Humanos , Hipertrofia/complicaciones , Hipertrofia/inmunología , Hipertrofia/patología , Interleucina-10/sangre , Interleucina-17/sangre , Recuento de Linfocitos , Masculino , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/genética , Tamaño de los Órganos , Rinitis Alérgica/complicaciones , Apnea Obstructiva del Sueño/complicaciones , Linfocitos T Reguladores/metabolismo , Células Th17/metabolismo , Factor de Crecimiento Transformador beta/sangreRESUMEN
The article contains the information about pro- and anti-inflammatory cytokines in infants with acute obstructive bronchitis and thymus hypertrophy. The content of IL-6 and IL-10 has been de- termined in 101 children in acute period of disease and during early convalescence. It was found the increasing of production of proinflammatory IL-6 and a low level of anti-inflammatory IL-10 in the first days of illness in all children with thymomegalia. During convalescence in patients with acute obstructive bronchitis and thymomegalia IL-6 level was decreasing, and the level of IL-10 was in- creasing, but it did not amount to the level of healthy children.