RESUMO
It is known that growth hormone (GH) is expressed in immune cells, where it exerts immunomodulatory effects. However, the mechanisms of expression and release of GH in the immune system remain unclear. We analyzed the effect of growth hormone-releasing hormone (GHRH), thyrotropin-releasing hormone (TRH), ghrelin (GHRL), and somatostatin (SST) upon GH mRNA expression, intracellular and released GH, Ser133-phosphorylation of CREB (pCREBS133), intracellular Ca2+ levels, as well as B-cell activating factor (BAFF) mRNA expression in bursal B-lymphocytes (BBLs) cell cultures since several GH secretagogues, as well as their corresponding receptors (-R), are expressed in B-lymphocytes of several species. The expression of TRH/TRH-R, ghrelin/GHS-R1a, and SST/SST-Rs (Subtypes 1 to 5) was observed in BBLs by RT-PCR and immunocytochemistry (ICC), whereas GHRH/GHRH-R were absent in these cells. We found that TRH treatment significantly increased local GH mRNA expression and CREB phosphorylation. Conversely, SST decreased GH mRNA expression. Additionally, when added together, SST prevented TRH-induced GH mRNA expression, but no changes were observed in pCREBS133 levels. Furthermore, TRH stimulated GH release to the culture media, while SST increased the intracellular content of this hormone. Interestingly, SST inhibited TRH-induced GH release in a dose-dependent manner. The coaddition of TRH and SST decreased the intracellular content of GH. After 10 min. of incubation with either TRH or SST, the intracellular calcium levels significantly decreased, but they were increased at 60 min. However, the combined treatment with both peptides maintained the Ca2+ levels reduced up to 60-min. of incubation. On the other hand, BAFF cytokine mRNA expression was significantly increased by TRH administration. Altogether, our results suggest that TRH and SST are implicated in the regulation of GH expression and release in BBL cultures, which also involve changes in pCREBS133 and intracellular Ca2+ concentration. It is likely that TRH, SST, and GH exert autocrine/paracrine immunomodulatory actions and participate in the maturation of chicken BBLs.
Assuntos
Proteínas Aviárias/imunologia , Linfócitos B/imunologia , Bolsa de Fabricius/imunologia , Galinhas/imunologia , Grelina/imunologia , Hormônio Liberador de Hormônio do Crescimento/imunologia , Hormônio do Crescimento/imunologia , Somatostatina/imunologia , Hormônio Liberador de Tireotropina/imunologia , Animais , Linfócitos B/citologia , Bolsa de Fabricius/citologia , Técnicas de Cultura de Células , Células CultivadasRESUMO
Obesity and insulin resistance have reached epidemic proportions. Obesogenic conditions are associated with increased risk for the development of other comorbidities and obesity-related diseases. In metabolic disorders, there is chronic low-grade inflammation induced by the activation of immune cells, especially in metabolic relevant organs such as white adipose tissue (WAT). These immune cells are regulated by environmental and systemic cues. Ghrelin is a peptide secreted mainly by X/A-like gastric cells and acts through the growth hormone secretagogue receptor (GHS-R). This receptor is broadly expressed in the central nervous system (CNS) and in several cell types, including immune cells. Studies show that ghrelin induces an orexigenic state, and there is increasing evidence implicating an immunoregulatory role for ghrelin. Ghrelin mainly acts on the innate and adaptive immune systems to suppress inflammation and induce an anti-inflammatory profile. In this review, we discuss the immunoregulatory roles of ghrelin, the mechanisms by which ghrelin acts and potential pharmacological applications for ghrelin in the treatment of obesity-associated inflammatory diseases, such as type 2 diabetes (T2D).
Assuntos
Imunidade Adaptativa , Grelina/imunologia , Sistema Imunitário/imunologia , Imunidade Inata , Inflamação/imunologia , Obesidade/imunologia , Animais , Anti-Inflamatórios/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/imunologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Grelina/metabolismo , Grelina/uso terapêutico , Humanos , Hipoglicemiantes/uso terapêutico , Sistema Imunitário/efeitos dos fármacos , Sistema Imunitário/metabolismo , Sistema Imunitário/fisiopatologia , Inflamação/metabolismo , Inflamação/fisiopatologia , Inflamação/prevenção & controle , Resistência à Insulina , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Obesidade/fisiopatologia , Receptores de Grelina/imunologia , Receptores de Grelina/metabolismo , Transdução de SinaisRESUMO
Modern subunit vaccines have excellent safety profiles and improved tolerability, but do not elicit strong immune responses without the addition of adjuvants. Developing a safe and affective adjuvant remains a challenge for peptide-based vaccine design. Growth Hormone Releasing Peptide-6 (GHRP-6) is one of the earliest-developed, synthetic, peptidyl growth hormone secretagogue receptor agonists. These compounds mimic the effect of the endogenous ligand, ghrelin. In the present study, we evaluated the ability of GHRP-6 to enhance the humoral immune response against co-injected antigens in mice, tilapia and African catfish. This peptide was able to increase the antigen-specific antibody response using heterologous proteins and peptides as antigens, which were also formulated in "water in oil" emulsions (Freund and Montanide). As long as we know there is no previous report describing any ghrelin analogous as molecular immunomodulator stimulating a humoral immune response. Further studies will be conducted to evaluate the functionality of this humoral immune response in challenge trials.