title: Signaling events leading to peroxiredoxin 5 up-regulation in immunostimulated macrophages.
abstract: Peroxiredoxins (PRXs) are thiol peroxidases associated with many cellular functions including proliferation, cell cycle, apoptosis, and differentiation. There is also increasing evidence that these ubiquitous antioxidant enzymes control H(2)O(2) signaling in eukaryotes. Here, we provide evidence that the LPS/TLR4 and the Th1 cytokine IFN-gamma pathways induce expression of PRX5, a potent peroxide and peroxynitrite reductase, in primary macrophages. Furthermore, deletion of TRIF, MyD88, or type I IFN receptor revealed that the LPS/TLR4-dependent increase in PRX5 expression is mediated by a TRIF-dependent/IFN-beta-independent pathway. IFN-gamma-dependent induction of the PRX5 gene was markedly reduced in MyD88(-/-) and TNF(-/-) macrophages. Moreover, addition of exogenous TNF allowed the recovery of full PRX5 expression in both MyD88(-/-) and TNF(-/-) cells stimulated with IFN-gamma, suggesting that basal TNF produced in an MyD88-dependent manner contributes to PRX5 induction. Downstream of the TLR pathways, we have explored the role of MAPK activation and found that p38 and JNK mainly contribute to PRX5 up-regulation in immunostimulated macrophages. Expression of PRX5 is thus responsive to innate immunity signals, and we propose that PRX5 is an additional host defense weapon of activated macrophages.
authors.affiliation: Institut de Chimie des Substances Naturelles, CNRS UPR2301, 91190 Gif-sur-Yvette, France.
authors.forename: Kahina
authors.initials: K
authors.lastname: Abbas
authors.forename: Jacques
authors.initials: J
authors.lastname: Breton
authors.forename: Cédric R
authors.initials: CR
authors.lastname: Picot
authors.forename: Valérie
authors.initials: V
authors.lastname: Quesniaux
authors.forename: Cécile
authors.initials: C
authors.lastname: Bouton
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Drapier
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics; D000818:Animals; D002478:Cells, Cultured; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D054464:Peroxiredoxins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D017471:Receptors, Interferon / Q000235:genetics; D015398:Signal Transduction / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D007371:Interferon-gamma; D008070:Lipopolysaccharides; D048670:MAP Kinase Kinase 4; D053594:Myeloid Differentiation Factor 88; D052247:Nitric Oxide Synthase Type II; D054464:Peroxiredoxins; D017471:Receptors, Interferon; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases; C507780:Myd88 protein, mouse; C476286:Ticam1 protein, mouse; C493487:Tlr4 protein, mouse; C496317:Nos2 protein, mouse