6.3 - α-MSH and bacterial infections
Despite viral infections, the literature provides solid evidence demonstrating the antibacterial capacity of α-MSH and its derived peptides. Several derived peptides and analog molecules of α-MSH have shown effectiveness against E. coli, Methicillin-resistantStaphylococcus aureus (MRSA), and S. aureus (please refer to Supplementary Table 2 for specific references). In terms of the molecule’s pro-resolutive effects, research has found that α-MSH treatment leads to a decrease in the phagocytosis of unopsonizedE. coli and S. aureus , inhibition of NO production by RAW 264.7 cells, downregulation of TLR2 expression induced by S. aureus , and a reduction in IL-6 levels while mitigating fever induced by LPS in rats (Phan and Taylor, 2013; Star et al., 1995; Ryu et al., 2015; Huang and et al, 1998). In a mouse peritonitis model, administration of the agonist AP214 prior to zymosan injection inhibited cell infiltration via MC3R. In vitro experiments also demonstrated that AP214 reduced the release of TNF, IL-6, and IL-1β by primary peritoneal macrophages stimulated with zymosan via MC3R. However, it is important to note that AP214 stimulated the uptake of zymosan particles and apoptotic neutrophils by macrophages (Montero-Melendez et al., 2011). These studies strongly suggest that both α-MSH and its agonist exert pro-resolutive effects against bacterial infections, and these effects may be mediated by MC3R.