RESUMEN
Levels of the melanocortin receptor (MCR) 1, 2, 3 and 5 subtypes and pro-opio-melanocortin (POMC) protein mRNA were measured by the real-time quantitative reverse transcriptase polymerase chain reaction method in CD4+ T helper (Th) cells, CD8+ T cytotoxic cells, CD19+ B cells, CD56+ natural killer (NK) cells, CD14+ monocytes and CD15+ granulocytes from healthy donors. We found high levels of all of the MC1, 2, 3 and 5R subtype mRNA in Th cells and moderate levels in NK cells, monocytes and granulocytes. POMC peptide mRNA was found in all examined leucocyte subsets, but only low levels were present in granulocytes. Our findings suggest a co-ordinating role for MCR subtypes and their naturally occurring ligands in the co-operation between innate and adaptive immunity. Moreover, our findings are compatible with earlier finding of MCR-mediated tolerance induction in Th cells.
Asunto(s)
Leucocitos/metabolismo , Proopiomelanocortina/genética , Receptores de Melanocortina/genética , Adulto , Linfocitos B/metabolismo , Secuencia de Bases , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD8-positivos/metabolismo , ADN Complementario/genética , Expresión Génica , Granulocitos/metabolismo , Humanos , Células Asesinas Naturales/metabolismo , Leucocitos/clasificación , Monocitos/metabolismo , ARN Mensajero/sangre , ARN Mensajero/genética , Receptor de Melanocortina Tipo 1/genética , Receptor de Melanocortina Tipo 2/genética , Receptor de Melanocortina Tipo 3/genética , Receptores de Corticotropina/genética , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
The melanocortin receptors exist in five subtypes, MC(1-5)R. These receptors participate in important regulations of the immune system, central behavior, and endocrine and exocrine glands. Here we provide a short review on MCR subtype selective peptides and organic compounds with activity on the MCRs, developed in our laboratory. Also provided is an overview of our new proteochemometric modeling technology, which has been applied to model the interaction of MSH peptides with the MCRs.
Asunto(s)
Modelos Biológicos , Isoformas de Proteínas/metabolismo , Receptores de Corticotropina/metabolismo , Humanos , Ligandos , Hormonas Estimuladoras de los Melanocitos/química , Hormonas Estimuladoras de los Melanocitos/metabolismo , Péptidos/química , Péptidos/metabolismo , Isoformas de Proteínas/química , Receptores de Corticotropina/química , Receptores de MelanocortinaRESUMEN
The expression of melanocortin MC(1) receptors on human peripheral lymphocyte subsets was analysed by flow cytometry using rabbit antibodies selective for the human MC(1) receptor and a panel of monoclonal antibodies against lymphocyte differentiation markers. The MC(1) receptor was found to be constitutively expressed on monocytes/macrophages, B-lymphocytes, natural killer (NK) cells and a subset of cytotoxic T-cells. Interestingly T-helper cells appeared to be essentially devoid of MC(1) receptors. The results were confirmed by RT-PCR which indicated strong expression of MC(1) receptor mRNA in CD14(+), CD19(+) and CD56(+) cells. However, only a faint RT-PCR signal was seen in CD3(+) cells, in line with the immuno-staining results that indicated that only part of the CD3(+) cells (i.e. some of the CD8(+) cells) expressed the MC(1) receptor. The MC(1) receptors' constitutive expression on immune cells with antigen-presenting and cytotoxic functions implies important roles for the melanocortic system in the modulation of immune responses.
Asunto(s)
Células Presentadoras de Antígenos/inmunología , Células Presentadoras de Antígenos/metabolismo , Leucocitos/inmunología , Leucocitos/metabolismo , Receptores de Corticotropina/genética , Receptores de Corticotropina/metabolismo , Linfocitos T Citotóxicos/inmunología , Linfocitos T Citotóxicos/metabolismo , Adulto , Animales , Linfocitos B/inmunología , Linfocitos B/metabolismo , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Expresión Génica , Humanos , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Conejos , Receptores de Melanocortina , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismoRESUMEN
Strong evidence suggests a functional link between the melanocortin and dopamine systems. alpha-Melanocyte stimulating hormone (alpha-MSH) induced grooming behaviour, which can be blocked by dopamine receptor antagonists, is associated with increased dopaminergic transmission in the striatal regions. Whether this effect is mediated specifically by melanocortin (MC) receptors has not previously been established. Using in vivo microdialysis on anesthesized rats we have shown that alpha- MSH administered into the ventral tegmental area induced a significant increase in dopamine and DOPAC levels in the nucleus accumbens. This increase was completely blocked by pre-treatment with the MC4 receptor selective antagonist HS131, indicating that the effects of alpha-MSH on dopamine transmission may be mediated by the MC4 receptor.
Asunto(s)
Dopamina/metabolismo , Núcleo Accumbens/efectos de los fármacos , Núcleo Accumbens/metabolismo , Receptores de Corticotropina/fisiología , alfa-MSH/farmacología , Animales , Células COS , Relación Dosis-Respuesta a Droga , Aseo Animal/efectos de los fármacos , Aseo Animal/fisiología , Masculino , Ensayo de Unión Radioligante , Ratas , Ratas Sprague-Dawley , Receptor de Melanocortina Tipo 4 , Receptores de Corticotropina/metabolismo , Área Tegmental Ventral/efectos de los fármacos , Área Tegmental Ventral/metabolismoRESUMEN
It has been established that the complex systemic and local administration of human ECHO-7 virus exerts an inhibitory effect on the growth of MX-17 tumour in the BALB/c mice without the signs of viral oncolysis. The antitumour effect is due to a modulation of the antitumour immunity (immunological regression) against a background of the viral immunogenesis.
