کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1909752 | 1046739 | 2010 | 11 صفحه PDF | دانلود رایگان |
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 IFNγ 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 IFNγ 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 IFNγ-induced gene expression of Prx 6 was also regulated in an NO-independent manner by cyclooxygenases and prostaglandin E2. Taken together our results indicate a possible role for Prxs in defense mechanisms of activated macrophages against oxidative stress during inflammation or infection.
Journal: Free Radical Biology and Medicine - Volume 49, Issue 12, 15 December 2010, Pages 1881–1891