RESUMEN
Immune cells are bioenergetically expensive during activation, which requires tightly regulated control of metabolic pathways. Both low and high glycemic conditions can modulate immune function. States of undernourishment depress the immune system, and in the same way, excessive intake of nutrients, such as an obesity state, compromise its functioning. Multicellular organisms depend on two mechanisms to survive: the regulation and ability to store energy to prevent starvation and the ability to fight against infection. Synergic interactions between metabolism and immunity affect many systems underpinning human health. In a chronic way, the breakdown of glycemic homeostasis in the body can influence cells of the immune system and consequently contribute to the onset of diseases such as type II diabetes, obesity, Alzheimer's, and fat and lean mass loss. On the contrary, exercise, recognized as a primary strategy to control hyperglycemic disorders, also induces a coordinated immune-neuro-endocrine response that acutely modulates cardiovascular, respiratory, and muscle functions and the immune response to exercise is widely dependent on the intensity and volume that may affect an immunodepressive state. These altered immune responses induced by exercise are modulated through the "stress hormones" adrenaline and cortisol, which are a threat to leukocyte metabolism. In this context, carbohydrates appear to have a positive acute response as a strategy to prevent depression of the immune system by maintaining plasma glucose concentrations to meet the energy demand from all systems involved during strenuous exercises. Therefore, herein, we discuss the mechanisms through which exercise may promotes changes on glycemic homeostasis in the metabolism and how it affects immune cell functions under higher or lower glucose conditions.
Asunto(s)
Diabetes Mellitus Tipo 2/metabolismo , Ejercicio Físico/fisiología , Glucosa/metabolismo , Homeostasis/fisiología , Glucosa/inmunología , Homeostasis/inmunología , Hormonas/inmunología , Hormonas/metabolismo , Humanos , Sistema Inmunológico/metabolismoRESUMEN
Emerging data suggest that elevated glucose may promote inflammatory activation of monocytic lineage cells with the ability to injure vascular endothelial tissue of diabetic patients, however evidence in primary human monocytes and macrophages is still insufficient. We investigated the effect of high glucose concentration on the inflammatory capacity of human macrophages in vitro and examined whether similar responses were detectable in circulating monocytes from prediabetic patients. Primary monocytes were isolated from healthy blood donors and differentiated into macrophages. Differentiated macrophages were exposed to normal levels of glucose (NG), high glucose (HG) or high mannitol as osmotic pressure control (OP) for three days. Using PCR, ELISA and flow cytometry, we found that HG macrophages showed overexpression of CD11c and inducible nitric oxide synthase as well as down-regulation of arginase-1 and interleukin (IL)-10 with respect to NG and OP macrophages. Consistent with in vitro results, circulating monocytes from hyperglycemic patients exhibited higher levels of CD11c and lower expression of CD206 than monocytes from normoglycemic controls. In subjects with hyperglycemia, elevation in CD11c(+) monocytes was associated with increased obesity, insulin resistance, and triglyceridemia as well as low serum IL-10. Our data suggest that human monocytes and macrophages undergo M1-like inflammatory polarization when exposed to high levels of glucose on in vitro culture conditions and in patients with hyperglycemia. These results demonstrate that excess glucose has direct effects on macrophage activation though the molecular mechanisms mediating such a response remain to be elucidated.
Asunto(s)
Glucosa/metabolismo , Hiperglucemia/inmunología , Macrófagos/inmunología , Arginasa/metabolismo , Antígeno CD11c/metabolismo , Diferenciación Celular , Células Cultivadas , Citocinas/metabolismo , Glucosa/inmunología , Humanos , Interleucina-10/metabolismo , Manitol/metabolismo , Monocitos/inmunología , Óxido Nítrico Sintasa de Tipo II/metabolismo , Cultivo Primario de Células , Células TH1/inmunologíaRESUMEN
BACKGROUND: The aim of this study was to evaluate the biochemical and immunological characteristics of saliva from diabetic patients compared to non-diabetic adults. METHODS: Eighty-eight diabetic adults and 39 non-diabetic adults (control) were included in the study. Glucose, urea, calcium, total protein and amylase were determined by a colorimetric method. The levels of secretory IgA and the IgA anti-Streptococcus mutans and anti-insulin IgA antibodies were measured by enzyme-linked immunosorbent assay (ELISA). Caries status was evaluated using the DMFT index. RESULTS: Glucose, urea, calcium, anti-S. mutans IgA, total IgA, and anti-insulin IgA were significantly higher in diabetic patients, whereas total protein and amylase levels were lower in these patients. There was no positive correlation between blood and salivary glucose levels in either group. Diabetic patients had a higher DMFT index. CONCLUSIONS: The present study showed for the first time that IgA levels in diabetic patients'saliva, shows correlation with systemic biochemical parameters. Thus the saliva is an useful tool to follow the systemic health status in these patients.
Asunto(s)
Caries Dental/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Saliva/química , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Amilasas/análisis , Amilasas/inmunología , Anticuerpos Antibacterianos/análisis , Calcio/análisis , Estudios de Casos y Controles , Caries Dental/complicaciones , Caries Dental/inmunología , Caries Dental/patología , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/inmunología , Diabetes Mellitus Tipo 1/patología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/inmunología , Diabetes Mellitus Tipo 2/patología , Femenino , Glucosa/análisis , Glucosa/inmunología , Humanos , Inmunoglobulina A Secretora/análisis , Insulina/análisis , Insulina/inmunología , Masculino , Persona de Mediana Edad , Saliva/inmunología , Proteínas y Péptidos Salivales/análisis , Proteínas y Péptidos Salivales/inmunología , Streptococcus mutans/inmunología , Urea/análisis , Urea/inmunologíaRESUMEN
An inflammatory response induced by high glucose is a cause of endothelial dysfunction in diabetes and is an important contributing link to atherosclerosis. Diabetes is an independent risk factor of atherosclerosis and activation of retinoid X receptor (RXR) has been shown to exert anti-atherogenic effects. In the present study, we examined the effects of the RXR ligands 9-cis-retinoic acid (9-cis-RA) and SR11237 on high glucose-induced inflammation in human umbilical endothelial vein endothelial cells (HUVECs) and explored the potential mechanism. Our results showed that the inflammation induced by high-glucose in HUVECs was mainly mediated by the activation of nuclear factor-B (NF- κB). High glucose-induced expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were in comparison, significantly decreased by treatment with RXR. The effect of RXR agonists was mainly due to the inhibition of NF-κB activation. Using pharmacological inhibitors and siRNA, we confirmed that nicotinamide adenine dinucleotide phosphate (NADPH) oxidase was an upstream activator of NF-κB. Furthermore, RXR agonists significantly inhibited high glucose-induced activation of NADPH oxidase and significantly decreased the production of reactive oxygen species (ROS). To explore whether the rapid inhibitory effects of RXR agonists were in fact mediated by RXR, we examined the effect of RXR downregulation by RXR siRNA. Our results showed that RXR siRNA largely abrogated the effects of RXR agonists, suggesting the requirement of RXR expression. Therefore, we have shown that RXR is involved in the regulation of NADPH oxidase- NF-κB signal pathway, as the RXR ligands antagonized the inflammatory response in HUVECs induced by high glucose.
Asunto(s)
Glucosa/farmacología , Inflamación/inmunología , NADPH Oxidasas/antagonistas & inhibidores , Receptores X Retinoide/agonistas , Factor de Transcripción ReIA/antagonistas & inhibidores , Alitretinoína , Antineoplásicos/farmacología , Aterosclerosis , Benzoatos/farmacología , Células Cultivadas , Diabetes Mellitus , Endotelio Vascular/citología , Endotelio Vascular/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Glucosa/inmunología , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Inflamación/tratamiento farmacológico , Molécula 1 de Adhesión Intercelular/biosíntesis , NADPH Oxidasa 4 , NADPH Oxidasas/genética , Interferencia de ARN , ARN Interferente Pequeño , Especies Reactivas de Oxígeno/metabolismo , Receptores X Retinoide/genética , Receptores X Retinoide/farmacología , Retinoides/farmacología , Tretinoina/farmacología , Regulación hacia Arriba , Molécula 1 de Adhesión Celular Vascular/biosíntesisRESUMEN
Matrinxã (Brycon amazonicus) is a freshwater neotropical fish species with a social interaction and aggressive behavior, especially in crowded environments. This species' social structure is established by agonistic interactions, which increase significantly at the fifth hour, when compared to the first and second hours of confinement, when each dominant fish competes with other individual for a conditioned territorialism. This social relationship also induces a complex physiological response in the organism, which generates an acute stimulation from the stressor agent. A stress situation modulates the physiology of the subordinate fish, which undergo significant increases in cortisol, glucose, hematocrit, and hemoglobin, when compared to the control fish. The immune system also indicates a modulation caused by cortisol, which results in an increase in neutrophils and a significant decrease in thrombocytes in subordinate fish, in comparison with control fish; however, the dominant fish show a significant increase in monocytes and a decrease in lymphocyte levels, when compared control fish. The agonistic interactions in B. amazonicus during crowding are not favorable to the physiology and immune system of the fish, mainly subordinate fish, and should be avoided in rearing systems.
Asunto(s)
Agresión/fisiología , Conducta Animal/fisiología , Peces/fisiología , Estrés Fisiológico/inmunología , Animales , Glucosa/inmunología , Hematócrito , Hemoglobinas/inmunología , Hidrocortisona/inmunología , Recuento de Leucocitos , Especificidad de la EspecieRESUMEN
Increasing evidence suggests that in Chagas' disease chronic-phase pathology is autoimmune in nature. There are at least two nonexclusive explanations for the generation of autoimmunity in Chagas disease: a) infection with the parasite perturbs immunoregulation, leading to loss of tolerance for self-antigens; b) immune recognition of T. cruzi antigens is crossreactive with selected mammalian antigens, leading to autoimmunity (molecular mimicry). Through this latter mechanism, T. cruzi antigens that share epitopes with mammalian nervous tissue may drive autoreactive B- or T-cell clones to expand and cause autoimmune lesions in chronic chagasic patients. Several different antigens sharing this characteristic have been studied, as for example the 160-kDa flagellum-associated surface protein (Fl-160), which has a nervous tissue crossreactive epitope composed by twelve amino acids. Additionally, it has been demonstrated that a trypomastigote stage-specific 85kDa surface glycoprotein (Gp85) has terminal galactosyl(alpha 1-3)galactose terminal residues, which are reactive with chronic chagasic sera. Common glycolipid antigens have also been reported, as for example galactocerebroside, sulfogalactocerebroside and sulfoglucuronylcerebroside, all of them specifically present at high concentrations in mammalian nervous system and in T. cruzi trypomastigotes. Chronic chagasic patients produce elevated levels of antibodies against these three glycolipid antigens. They also do against terminal galactosyl(alpha 1-3)galactose residues present on several acid and neutral glycolipids common either to nervous system or parasite. These antibodies are powerful lytic for circulating T. cruzi trypomastigotes. Another common strongly immunogenic residues are galactosyl(alpha 1-2)galactose, galactosyl(alpha 1-6)galactose and galactofuranosyl(beta 1-3)mannose residues present on several glycoinositolphospholipids (GIPL), against which chronic chagasic patients have elevated levels of specific antibodies. In brief, very specific host-parasite relationships existing only in Chagas' disease may explain the particular peripheral nervous tissue damage seen in acute or chronic stages of this disease. This specificity could depend either on invasion of autonomic ganglia by T. cruzi trypomastigotes and modification of nervous cell surface structures by some of the several mechanisms of acquired molecular mimicry.