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Effect of ppMCH derived peptides on PBMC proliferation and cytokine expression
Bernard Coumans1, Thierry Grisar, Jean-Louis Nahon
1Center for Cellular and Molecular Neurobiology, University of Liège, Liège, Belgium.
Abstract:
The mRNA encoding prepro-Melanin concentrating hormone (ppMCH) is mainly expressed in the central nervous system but has also been detected at lower amount in many peripheral tissues including spleen and thymus. At the peptide level however, several forms of the precursor can be detected in these tissues and are sometimes expressed at similar levels compared to brain. In the present work, we have studied the in vitro action of a wide range of concentration (1 nM to 1 microM) of the different peptides encoded by ppMCH i.e. neuropeptide glycine-glutamic acid (NGE), neuropeptide glutamic acid-isoleucine (NEI), Melanin concentrating hormone (MCH) and the dipeptide NEI-MCH on peripheral blood mononuclear cells (PBMC) proliferation and cytokine production following anti-CD3 stimulation. Among them only MCH decreased PBMC proliferation with a maximal effect of 35% at 100 nM. Moreover as demonstrated by using ELISA, MCH significantly decreases IL-2 production by 25% but not IL-4, INF-gamma or TNF-alpha expression. Interestingly, exogenous IL-2 decreases significantly MCH-mediated inhibition, suggesting that it is an important downstream mediator of MCH action. Finally, we showed that after 7 to 9 days of incubation, MCH also inhibits proliferation of non-stimulated PBMC. Altogether, these data demonstrate that fully mature MCH modulates proliferation of anti-CD3 stimulated PBMC partially through regulation of IL-2 production.
Insights
Melanin concentrating hormone (MCH) inhibits peripheral blood mononuclear cell (PBMC) proliferation and IL-2 production. This immune modulation by MCH occurs in both stimulated and non-stimulated cells, highlighting its role in immune responses.
Area of Science:
- Immunology
- Neuroendocrinology
Background:
- Prepro-Melanin concentrating hormone (ppMCH) mRNA is found in the central nervous system and peripheral tissues like spleen and thymus.
- Several ppMCH-derived peptides exist, with some showing significant expression in peripheral tissues.
Purpose of the Study:
- To investigate the in vitro effects of ppMCH-encoded peptides on peripheral blood mononuclear cell (PBMC) proliferation and cytokine production.
- To determine the specific role of Melanin concentrating hormone (MCH) in immune cell modulation.
Main Methods:
- Incubation of PBMCs with varying concentrations (1 nM to 1 microM) of NGE, NEI, MCH, and NEI-MCH peptides.
- Assessment of PBMC proliferation and cytokine production (IL-2, IL-4, INF-gamma, TNF-alpha) following anti-CD3 stimulation.
- Evaluation of exogenous IL-2's effect on MCH-mediated inhibition.
Main Results:
- Only MCH significantly decreased anti-CD3 stimulated PBMC proliferation by up to 35% at 100 nM.
- MCH significantly reduced IL-2 production by 25% but did not affect IL-4, INF-gamma, or TNF-alpha.
- Exogenous IL-2 partially reversed MCH-induced inhibition, indicating IL-2's role as a downstream mediator.
- MCH also inhibited proliferation of non-stimulated PBMCs after prolonged incubation (7-9 days).
Conclusions:
- Mature MCH modulates the proliferation of anti-CD3 stimulated PBMCs.
- MCH's immunomodulatory effect is partly mediated through the regulation of IL-2 production.
- MCH exhibits inhibitory effects on both stimulated and non-stimulated immune cells in vitro.
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