beta-MSH inhibits brain inflammation via MC sub(3)/ sub(4) receptors and impaired NF- Kappa B signaling

The anti-inflammatory effects of melanocortin peptides have been demonstrated in different inflammation models. This is the first report describing the molecular mechanisms for the beta -MSH-induced suppression of bacterial lipopolisaccharide (LPS)-caused brain inflammation. We found that beta -MSH suppresses LPS-induced nuclear translocation of the transcription factor NF- Kappa B, and inhibits the expression of inducible nitric oxide synthase, and the following nitric oxide overproduction in the brain, in vivo. Moreover, administering the preferentially MC sub(4) receptor selective antagonist HS014 blocked completely these effects, suggesting a tentative MC sub(4) receptor mediated mechanism of action for the beta -MSH. However, as HS014 shows quite low selectivity vis-a-vis the MC sub(3) receptor, a role for the MC sub(3) receptor cannot be excluded. In conclusion, our results show that beta -MSH is capable of inhibiting brain inflammation via activation of melanocortin receptors, of the subtypes 4 and/or 3.