FS145 exerts anti-inflammatory and analgesic effects through blocking integrin αvβ3 on macrophages

Macrophages exert a crucial role in the initiation and regulation of inflammation, and certain proteins derived from the saliva of blood-feeding arthropods have been proven to have potent anti-inflammatory and analgesic properties by regulating macrophages’ functions. We previously identified and characterized FS145, a disintegrin from the saliva of the flea Xenopsylla cheopis, which was demonstrated as an antiangiogenesis factor in vivo and in vitro by specific blockage of the integrin α_vβ₃ function. Here, we investigated its anti-inflammatory and analgesic effects as well as the molecular mechanism of action of this ectoparasitic peptide. FS145 could bind to RAW264.7 cells at a concentration-dependent manner and significantly attenuate the adhesion of LPS-activated RAW264.7 cells to fibrinogen, fibronectin, and vitronectin but not to laminin. Furthermore, FS145 was shown to inhibit macrophage migration and the production of NO, TNF-α, IL-1β and IL-6 by suppressing MAPK/NF-κB signaling cascades in LPS-induced macrophages. Notably, FS145 was also exhibited the potent anti-inflammatory and anti-nociceptive effects in vivo. These findings suggest that FS145 may exert a therapeutic effect by blocking integrin α_vβ₃ and suppressing MAPK/NF-κB ing pathways and the subsequent inflammatory response of macrophages. Therefore, FS145 holds promise as a novel anti-inflammatory and analgesic agent, warranting further investigation into its potential clinical applications.