Modulation of formyl peptide receptor 1 induced by Resveratrol in an LPS induced neuroinflammatory animal model.

The search of novel therapeutic agents for the management of neurodegenerative diseases has become an appealing research interest in recent years. Neuroinflammatory response within the brain or spinal cord is the production of several mediators, including cytokines, chemokines, reactive oxygen species and secondary messengers, released by resident glia cells. Although it may represent a neuroprotective mechanism a sustained neuroinflammation can induce neurotoxicity and is related to neurodegeneration [ Cianciulli A. et al. 2020]. The invading pathogens and their components are recognized by pattern recognition receptors (PRR) including the G-protein coupled formyl peptide receptors (FPRs), which are expressed by immune cells [ Bianchi M.E. 2007]. The murine FPR gene family includes at least six members in contrast to the only three in humans. The two most important members are the Fpr1 and Fpr2. Fpr1 encodes murine FPR1, which is considered the murine orthologue of human FPR. Resveratrol, a non-flavonoid polyphenol of the red wine and grapes, apart its beneficial health effects and anti-inflammatory properties, has been reported to reduce neuroinflammation in various neurodegenerative disease models. The anti-inflammatory responses of Resveratrol involve the activation of the protein deacetylase sirtuin 1 (SIRT1) gene. In this research we have investigated in an LPS based murine model of neuroinflammation the role of FPR1, examining not only if this receptor undergoes a reduction of its expression during neuroinflammation, but also whether treatment with Resveratrol was able to modulate its expression leading to an amelioration of neuroinflammatory picture. We have demonstrated that FPR1 together with SIRT1 resulted upregulated by Resveratrol treatment and that this increase is associated to a to reduction of neuroinflammatory responses. In this respect, different pro-inflammatory hallmarks such as IL-1β, IL-1βR, TNFα, TNFα-RI resulted downregulated by treatment of Resveratrol. In conclusion, the modulation of the FPR1 expression by Resveratrol may be evaluated not only to propose a novel anti-inflammatory and pro-resolving therapeutic target for the reduction of the detrimental effects of neuroinflammation in course of neurodegenerative diseases but also as promising approach to promote human health by a diet rich of antioxidative bioactive compounds.