IL-21 modulates release of proinflammatory cytokines in LPS-stimulated macrophages through distinct signaling pathways

Mediators Inflamm. 2013:2013:548073. doi: 10.1155/2013/548073. Epub 2013 Dec 26.

Abstract

The aim of this study was to investigate the anti-inflammatory effect of IL-21 on LPS-induced mouse peritoneal macrophages. The results showed that IL-21 significantly inhibited LPS-induced mRNA expression of IL-1β, TNF-α, and IL-6 in macrophages, but not of IFN-γ, IL-10, CCL5, or CXCL2. ELISA analysis showed that IL-21 also suppressed LPS-induced production of TNF-α and IL-6 in culture supernatants. Western blot analysis showed that IL-21 clearly inhibited ERK and IκBα phosphorylation and NF-κB translocation in LPS-stimulated macrophages, but it increased STAT3 phosphorylation. Flow cytometric and Western blot analysis showed that IL-21 decreased M1 macrophages surface markers expression of CD86, iNOS, and TLR4 in LPS-stimulated cells. All results suggested that IL-21 decreases IL-6 and TNF-α production via inhibiting the phosphorylation of ERK and translocation of NF-κB and promotes a shift from the M1 to M2 macrophage phenotype by decreasing the expression of CD86, iNOS, and TLR4 and by increasing STAT3 phosphorylation in LPS-stimulated cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B7-2 Antigen / metabolism
  • Cytokines / metabolism*
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Female
  • Flow Cytometry
  • Inflammation
  • Interleukin-1beta / metabolism
  • Interleukin-6 / metabolism
  • Interleukins / pharmacology*
  • Lipopolysaccharides
  • Macrophages / cytology
  • Macrophages / metabolism
  • Macrophages, Peritoneal / cytology*
  • Macrophages, Peritoneal / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Nitric Oxide Synthase Type II / metabolism
  • Phosphorylation
  • Real-Time Polymerase Chain Reaction
  • Recombinant Proteins / metabolism
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction*
  • Toll-Like Receptor 4 / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • B7-2 Antigen
  • Cytokines
  • Interleukin-1beta
  • Interleukin-6
  • Interleukins
  • Lipopolysaccharides
  • Recombinant Proteins
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide Synthase Type II
  • Extracellular Signal-Regulated MAP Kinases
  • interleukin-21