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Bast, A; Erttmann, SF; Walther, R; Steinmetz, I.
Influence of iNOS and COX on peroxiredoxin gene expression in primary macrophages.
Free Radic Biol Med. 2010; 49(12):1881-1891
Doi: 10.1016/j.freeradbiomed.2010.09.015
Web of Science
PubMed
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- Co-authors Med Uni Graz
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Steinmetz Ivo
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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 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.
Copyright © 2010 Elsevier Inc. All rights reserved.
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Interferon-gamma - pharmacology
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Cyclooxygenase
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iNOS
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JAK2
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Macrophage
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MAPK
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NADPH oxidase
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Peroxiredoxin
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PI3K
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Prostaglandin
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Free radicals