First Author | Bast A | Year | 2010 |
Journal | Free Radic Biol Med | Volume | 49 |
Issue | 12 | Pages | 1881-91 |
PubMed ID | 20869433 | Mgi Jnum | J:167094 |
Mgi Id | MGI:4867147 | Doi | 10.1016/j.freeradbiomed.2010.09.015 |
Citation | Bast A, et al. (2010) Influence of iNOS and COX on peroxiredoxin gene expression in primary macrophages. Free Radic Biol Med 49(12):1881-91 |
abstractText | Peroxiredoxins (Prxs) are a family of multifunctional antioxidant thiol-dependent peroxidases. This study aimed to examine the regulatory mechanisms of Prx gene expression in murine bone marrow-derived macrophages (BMMs) using standardized serum-free conditions. Stimulation with LPS and IFNgamma increased mRNA levels of Prx 1, 2, 4, 5, and 6 in BMMs of both C57BL/6 and BALB/c mice, with Prx 1, 2, 4, and 6 more strongly induced in C57BL/6 BMMs. Further investigations on signaling pathways in C57BL/6 BMMs demonstrated that up-regulation of Prx 5 and 6 by LPS and IFNgamma was associated with the activation of multiple protein kinases, most notably JAK2, PI3K, and p38 MAPK. Our experiments also revealed a contribution of inducible NO synthase-derived nitric oxide to the increase in Prx 1, 2, 4, and 6 mRNA expression, whereas NADPH oxidase-derived superoxide was not involved. Furthermore, we could show that LPS- and IFNgamma-induced gene expression of Prx 6 was also regulated in an NO-independent manner by cyclooxygenases and prostaglandin E(2). Taken together our results indicate a possible role for Prxs in defense mechanisms of activated macrophages against oxidative stress during inflammation or infection. |