Beta-MSH inhibits brain inflammation via MC₃/₄ receptors and impaired NF-κB 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 β-MSH-induced suppression of bacterial lipopolisaccharide (LPS)-caused brain inflammation. We found that β-MSH suppresses LPS-induced nuclear translocation of the transcription factor NF-κB, and inhibits the expression of inducible nitric oxide synthase, and the following nitric oxide overproduction in the brain, in vivo. Moreover, administering the preferentially MC₄ receptor selective antagonist HS014 blocked completely these effects, suggesting a tentative MC₄ receptor mediated mechanism of action for the β-MSH. However, as HS014 shows quite low selectivity vis-à-vis the MC ₃ receptor, a role for the MC₃ receptor cannot be excluded. In conclusion, our results show that β-MSH is capable of inhibiting brain inflammation via activation of melanocortin receptors, of the subtypes 4 and/or 3.