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 language | English (US) |
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Pages (from-to) | 411-419 |
Number of pages | 9 |
Journal | Microbiology and Immunology |
Volume | 56 |
Issue number | 6 |
DOIs | |
State | Published - Jun 2012 |
Externally published | Yes |
Keywords
- Interleukin-10
- Peroxiredoxin
- RAW264.7
- STAT3
ASJC Scopus subject areas
- Microbiology
- Immunology
- Virology