Modulation of IL-10 release and PPAR-gamma expression by an alpha-MSH analogue

LILA CARNIGLIA; CARLA CARUSO; DANIELA DURAND; MERCEDES LASAGA

Praga

Congreso; 10th European Meeting on Glial Cells in Health and Disease; 2011

Astrocytes and microglia play a major role in the regulation of the inflammatory response within the central nervous system. The alpha-melanocyte stimulating hormone(alpha-MSH) exerts immunomodulatory effects in diverse neuroinflammation models. We have previously shown that this neuropeptide exerts its anti-inflammatory actions in astrocytes through type 4 melanocortin receptors(MC4R). In this study we evaluated the effect of NDP-alpha-MSH (a synthetic analogue of alpha-MSH and MCR agonist) on the release of the anti-inflammatory cytokine interleukin-10 (IL-10) and the protein expression of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma, a nuclear receptor involved in the suppression of the inflammatory response) in rat primary cultured astrocytes and microglia. Treatment with NDP-alpha-MSH (10-8 – 10-5 M) for 24 hs induced a significant increase in IL-10 release from microglia, but not from astrocytes, as evaluated by ELISA (10-8 M: 79%*; 10-7 M: 140%**; 10-6 M: 122%**; 10-5 M: 103%** vs control)(*p below 0.05, **p below 0.01). In addition, 10-7 M NDP-alpha-MSH enhanced the expression of PPAR-gamma as evaluated by western blot in both cell types at 24 hs of treatment (2.3 times in astrocytes; 6.4 times in microglia)(p below 0.05) and this effect was prevented in the presence of an MC4R antagonist, HS024 (10-8 M). In conclusion, we propose that induction of IL-10 release and enhancement of PPAR-gamma protein expression might be involved in the overall anti-inflammatory effect of melanocortins in glial cells. 1. Caruso et al., 2007,Endocrinology, 148: 4918 – 4926.