Peroxiredoxin-1, a possible target in modulating inflammatory cytokine production in macrophage like cell line RAW264.7

Young Tae Lim, Dong Sup Song, Tae Joon Won, Yun Jung Lee, Jong Sun Yoo, Kyeong Eun Hyung, Joo Won Yoon, So Young Park, Kwang Woo Hwang

Research output: Contribution to journalArticlepeer-review

Abstract

Peroxiredoxin (PRX), a scavenger of H 2O 2 and alkyl hydroperoxides in living organisms, protects cells from oxidativestress. Contraryto its known anti-oxidantroles, the involvement ofPRX-1 in the regulation of lipopolysaccharide (LPS) signaling is poorly understood, possible immunological functions of PRX-1 having been uncovered only recently. In the present study, it was discovered that the PRX-1 deficient macrophage like cell line (RAW264.7) has anti-inflammatory activity when stimulated by LPS. Treatment with LPS for 3 hrs resulted in increased gene expression of an anti-inflammatory cytokine, interleukin-10 (IL-10), in PRX-1 knock down RAW264.7 cells. Gene expression of pro-inflammatory cytokines IL-1β and tumor necrosis factor- α (TNF-α) did not show notable changes under the same conditions. However, production of these cytokines significantly decreased in PRX-1 knock down RAW264.7 cells with 12 hrs of stimulation. Production of IL-10 was also increased in PRX-1 knock down RAW264.7 cells with 12 hrs of stimulation. We predicted that higher concentrations of IL-10 would result in decreased expression of IL-1β and TNF-α in PRX-1 knock-down cells. This was confirmed by blocking IL-10, which reestablished IL-1β and TNF-α secretion. We also observed that increased concentrations of IL-10 do not affect the NF-κB pathway. Interestingly, STAT3 phosphorylation by LPS stimulation was significantly increased in PRX-1 knockdown RAW264.7 cells. Up-regulation of IL-10 in PRX-1 knockdown cells and the resulting downregulation of proinflammatory cytokine production seem to involve the STAT3 pathway in macrophages. Thus, down-regulation of PRX-1 may contribute to the suppression of adverse effects caused by excessive activation of macrophages through affecting the STAT3 signaling pathway.

Original languageEnglish (US)
Pages (from-to)411-419
Number of pages9
JournalMicrobiology and Immunology
Volume56
Issue number6
DOIs
StatePublished - Jun 2012
Externally publishedYes

Keywords

  • Interleukin-10
  • Peroxiredoxin
  • RAW264.7
  • STAT3

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Virology

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