Influence of iNOS and COX on peroxiredoxin gene expression in primary macrophages.

Peroxiredoxins (Prxs) represent 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 (BMM) using standardized serum-free conditions. Stimulation with LPS and IFNgamma increased mRNA levels of Prx1, 2, 4, 5, and 6 in BMM of both C57BL/6 and BALB/c mice, with Prx 1, 2, 4, and 6 more strongly induced in C57BL/6 BMM. Further investigations on signaling pathways in C57BL/6 BMM demonstrated that up-regulation of Prx 5 and 6 by LPS and IFN was associated with the activation of multiple protein kinases, most notably JAK2, PI3K, and p38 MAPK. Our experiments also revealed a contribution of iNOS-derived nitric oxide to the increase of 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 Prx6 was also regulated in a NO-independent manner by cyclooxygenases and prostaglandin E(2). Taken together our results indicate a possible role of Prxs in defense mechanisms of activated macrophages against oxidative stress during inflammation and/or infection.