Activation of Nrf2/HO-1 by Peptide YD1 Attenuates Inflammatory Symptoms through Suppression of TLR4/MYyD88/NF-κB Signaling Cascade

Int J Mol Sci. 2021 May 13;22(10):5161. doi: 10.3390/ijms22105161.

Abstract

In this study, we investigate the immunomodulatory effects of a novel antimicrobial peptide, YD1, isolated from Kimchi, in both in vitro and in vivo models. We establish that YD1 exerts its anti-inflammatory effects via up-regulation of the Nrf2 pathway, resulting in the production of HO-1, which suppresses activation of the NF-κB pathway, including the subsequent proinflammatory cytokines IL-1β, IL-6, and TNF-α. We also found that YD1 robustly suppresses nitric oxide (NO) and prostaglandin E2 (PGE2) production by down-regulating the expression of the upstream genes, iNOS and COX-2, acting as a strong antioxidant. Collectively, YD1 exhibits vigorous anti-inflammatory and antioxidant activity, presenting it as an interesting potential therapeutic agent.

Keywords: AKT; MyD88; NF-κB; RAW 264.7; TLR-4; YD1; anti-inflammation; peptide drug.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Cytokines / metabolism
  • Edema / chemically induced
  • Edema / metabolism
  • Edema / pathology
  • Edema / prevention & control
  • Gene Expression Regulation / drug effects*
  • Heme Oxygenase-1 / genetics
  • Heme Oxygenase-1 / metabolism*
  • Inflammation / chemically induced
  • Inflammation / metabolism
  • Inflammation / pathology
  • Inflammation / prevention & control*
  • Lipopolysaccharides / toxicity
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Myeloid Differentiation Factor 88 / antagonists & inhibitors
  • Myeloid Differentiation Factor 88 / genetics
  • Myeloid Differentiation Factor 88 / metabolism
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism*
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Nitric Oxide / metabolism
  • Pore Forming Cytotoxic Proteins / pharmacology*
  • Toll-Like Receptor 4 / antagonists & inhibitors
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Lipopolysaccharides
  • Membrane Proteins
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • NF-E2-Related Factor 2
  • NF-kappa B
  • Nfe2l2 protein, mouse
  • Pore Forming Cytotoxic Proteins
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • Nitric Oxide
  • Heme Oxygenase-1
  • Hmox1 protein, mouse