Formyl Peptide Receptor (FPR)1 Modulation by Resveratrol in an LPS-Induced Neuroinflammatory Animal Model

Nutrients. 2021 Apr 23;13(5):1418. doi: 10.3390/nu13051418.

Abstract

Among therapeutic approaches that have been investigated, targeting of receptors implicated in managing neuroinflammation has been described. One such family of receptors comprises the formyl peptide receptors (FPRs) whose ligands could play a role in host defense. The murine FPR gene family includes at least six members while in humans there are only three. The two most important members are the Fpr1 and Fpr2. Fpr1encodes murine FPR1, which is considered the murine orthologue of human FPR. Resveratrol, a non-flavonoid polyphenol rich in red wine and grapes, apart from its beneficial health effects and anti-inflammatory properties, has been reported to reduce neuroinflammation in different neurodegenerative disease models. Resveratrol anti-inflammatory responses involve the activation of the protein deacetylase sirtuin 1 (SIRT1) gene. In this work 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 in a murine model of neuroinflammation. Results of this work showed that FPR1 together with SIRT1 resulted upregulated by resveratrol treatment and that this increase is associated with an amelioration of the neuroinflammatory picture, as demonstrated by the induction of IL-10 and IL1-RA expression and the downregulation of proinflammatory mediators, such as TNF-α and IL-1β. The expression and the modulation of FPR1 by resveratrol may be evaluated in order to propose a novel anti-inflammatory and pro-resolving therapeutic approach for the reduction of the detrimental effects associated with neuro-inflammation based neurodegenerative diseases and also as a promising strategy to promote human health by a diet rich in antioxidative bioactive compounds.

Keywords: FPR; microglia; neuroinflammation; nutrition; resveratrol.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Astrocytes / drug effects
  • Astrocytes / metabolism
  • Astrocytes / pathology*
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism
  • Disease Models, Animal
  • Glial Fibrillary Acidic Protein / metabolism
  • Inflammation / chemically induced
  • Inflammation / metabolism*
  • Inflammation / pathology*
  • Inflammation Mediators / metabolism
  • Interleukin 1 Receptor Antagonist Protein / metabolism
  • Lipopolysaccharides
  • Male
  • Mice
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism
  • Microglia / drug effects
  • Microglia / metabolism
  • Microglia / pathology*
  • Models, Biological
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Formyl Peptide / metabolism*
  • Resveratrol / pharmacology*
  • Signal Transduction
  • Sirtuin 1 / genetics
  • Sirtuin 1 / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Aif1 protein, mouse
  • Anti-Inflammatory Agents
  • Calcium-Binding Proteins
  • Glial Fibrillary Acidic Protein
  • Inflammation Mediators
  • Interleukin 1 Receptor Antagonist Protein
  • Lipopolysaccharides
  • Microfilament Proteins
  • RNA, Messenger
  • Receptors, Formyl Peptide
  • Tumor Necrosis Factor-alpha
  • Sirtuin 1
  • Resveratrol