Influence of iNOS and COX on peroxiredoxin gene expression in primary macrophages.
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.
Bast
Antje
A
Friedrich Loeffler Institute of Medical Microbiology, Ernst Moritz Arndt University of Greifswald, Greifswald, Germany. antje.bast@uni-greifswald.de
Erttmann
Saskia F
SF
Walther
Reinhard
R
Steinmetz
Ivo
I
D000818:Animals; D051545:Cyclooxygenase 1 / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D004789:Enzyme Activation; D007371:Interferon-gamma / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D019255:NADPH Oxidases / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D018384:Oxidative Stress; D054465:Peroxiredoxin VI / Q000235:genetics* / Q000378:metabolism; D054464:Peroxiredoxins / Q000235:genetics* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015854:Up-Regulation
D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; D007371:Interferon-gamma; D054465:Peroxiredoxin VI; D054464:Peroxiredoxins; D052247:Nitric Oxide Synthase Type II; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D019255:NADPH Oxidases; D015232:Dinoprostone