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.
- MSH peptides
Field of Science
- 3.1 Basic medicine
- 1.1. Scientific article indexed in Web of Science and/or Scopus database