Alpha-melanocyte-stimulating hormone suppresses antigen-induced lymphocyte proliferation in humans independently of melanocortin 1 receptor gene status
| Autor: | Ashley Cooper, Eugene Healy, Claire L. Jackson, Peter S. Friedmann, Samantha J. Robinson, Chris Pickard |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
medicine.medical_specialty
CD3 Complex Genotype Immunology Lymphocyte proliferation Biology Peripheral blood mononuclear cell Monocytes Cell Line chemistry.chemical_compound Mice Melanocortin receptor T-Lymphocyte Subsets Internal medicine medicine Immunology and Allergy Animals Humans Receptor Cell Proliferation Macrophages alpha-Melanocyte-stimulating hormone Growth Inhibitors Interleukin-10 Interleukin 10 Endocrinology chemistry alpha-MSH Melanocortin Receptor Melanocortin Type 1 Immunosuppressive Agents Melanocortin 1 receptor |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 175(7) |
| ISSN: | 0022-1767 |
| Popis: | Studies in mice indicate that α-melanocyte-stimulating hormone (αMSH) is immunosuppressive, but it is not known whether αMSH suppresses human immune responses to exogenous Ags. Human PBMCs, including monocytes, express the melanocortin 1 receptor (MC1R), and it is thought that the ability of αMSH to alter monocyte-costimulatory molecule expression and IL-10 release is mediated by this receptor. However, the MC1R gene is polymorphic, and certain MC1R variants compromise receptor signaling via cAMP, resulting in red hair and fair skin. Here, we have investigated whether αMSH can suppress Ag-induced lymphocyte proliferation in humans and whether these effects are dependent on MC1R genotype. αMSH suppressed streptokinase-streptodornase-induced lymphocyte proliferation, with maximal inhibition at 10−13–10−11 M αMSH. Anti-IL-10 Abs failed to prevent suppression by αMSH, indicating that it was not due to MC1R-mediated IL-10 release by monocytes. Despite variability in the degree of suppression between subjects, similar degrees of αMSH-induced immunosuppression were seen in individuals with wild-type, heterozygous variant, and homozygous/compound heterozygous variant MC1R alleles. RT-PCR of streptokinase-streptodornase-stimulated PBMCs for all five melanocortin receptors demonstrated MC1R expression by monocytes/macrophages, MC1R and MC3R expression by B lymphocytes, but no melanocortin receptor expression by T lymphocytes. In addition, αMSH did not significantly inhibit anti-CD3 Ab-induced lymphocyte proliferation, whereas αMSH and related analogs (SHU9119 and MTII) inhibited Ag-induced lymphocyte proliferation in monocyte-depleted and B lymphocyte-depleted assays. These findings demonstrate that αMSH, acting probably via MC1R on monocytes and B lymphocytes, and possibly also via MC3R on B lymphocytes, has immunosuppressive effects in humans but that suppression of Ag-induced lymphocyte proliferation by αMSH is independent of MC1R gene status. |
| Databáze: | OpenAIRE |
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