title: Peroxiredoxin-1, a possible target in modulating inflammatory cytokine production in macrophage like cell line RAW264.7.
abstract: Peroxiredoxin (PRX), a scavenger of H(2) O(2) and alkyl hydroperoxides in living organisms, protects cells from oxidative stress. Contrary to its known anti-oxidant roles, the involvement of PRX-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.
authors.affiliation: Laboratory of Host Defense Modulation, College of Pharmacy, Chung-Ang University, 221 Heukseok-dong, Dongjak-gu, Seoul, Korea.
authors.forename: Young
authors.initials: Y
authors.lastname: Tae Lim
authors.forename: Dong
authors.initials: D
authors.lastname: Sup Song
authors.forename: Tae
authors.initials: T
authors.lastname: Joon Won
authors.forename: Yun-Jung
authors.initials: YJ
authors.lastname: Lee
authors.forename: Jong-Sun
authors.initials: JS
authors.lastname: Yoo
authors.forename: Kyeong
authors.initials: K
authors.lastname: Eun Hyung
authors.forename: Joo
authors.initials: J
authors.lastname: Won Yoon
authors.forename: So-Young
authors.initials: SY
authors.lastname: Park
authors.forename: Kwang
authors.initials: K
authors.lastname: Woo Hwang
mesh_terms: D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D055785:Gene Knockdown Techniques; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D054464:Peroxiredoxins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D054464:Peroxiredoxins