HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Utsugi, M. Articles by Mori, M. Search for Related Content PubMed PubMed Citation Articles by Utsugi, M. Articles by Mori, M.

(Journal of Leukocyte Biology. 2002;71:339-347.)
© 2002 by Society for Leukocyte Biology

Glutathione redox regulates lipopolysaccharide-induced IL-12 production through p38 mitogen-activated protein kinase activation in human monocytes: role of glutathione redox in IFN- priming of IL-12 production

Mitsuyoshi Utsugi^*, Kunio Dobashi^*, Yasuhiko Koga^*, Yasuo Shimizu^*, Tamotsu Ishizuka^*, Kunihiko Iizuka^*, Junji Hamuro, Tsugio Nakazawa and Masatomo Mori^*

^* First Department of Internal Medicine, Faculty of Medicine, School of Medicine, and
Faculty of Health Sciences, Gunma University, Maebashi, Japan; and
Basic Research Laboratories, Ajinomoto Co., Kawasaki, Japan

Correspondence: Kunio Dobashi, M.D., Ph.D., First Department of Internal Medicine, Gunma University Faculty of Medicine, School of Medicine, 3-39-15 Showa-machi, Maebashi, Gunma, 371-8511, Japan. E-mail: dobashik{at}med.gunma-u.ac.jp

We examined whether changes in intracellular reduced (GSH) or oxidized (GSSG) glutathione of human monocytes regulate lipopolysaccharide (LPS)-induced IL-12 production and defined the molecular mechanism that underlies glutathione redox regulation. Monocytes exposed to glutathione reduced form ethyl ester (GSH-OEt) or maleic acid diethyl ester (DEM) increased or decreased the intracellular GSH/GSSG ratio, respectively. LPS-induced IL-12 production and p38 mitogen-activated protein (MAP) kinase activation were enhanced by GSH-OEt but suppressed by DEM. Selective p38 inhibitors showed that p38 promoted GSH-OEt-enhanced IL-12 production. Furthermore, IFN- priming increased the GSH/GSSG ratio and enhanced IL-12 production through p38, and DEM negated the priming effect of IFN- on p38 activation and IL-12 production as well as on the GSH/GSSG ratio. These findings reveal that glutathione redox regulates LPS-induced IL-12 production from monocytes through p38 MAP kinase activation and that the priming effect of IFN- on IL-12 production is partly a result of the glutathione redox balance.

Key Words: immune response • antigen-presenting cell • signal transduction

This article has been cited by other articles:

				C. Marantos, V. Mukaro, J. Ferrante, C. Hii, and A. Ferrante Inhibition of the Lipopolysaccharide-Induced Stimulation of the Members of the MAPK Family in Human Monocytes/Macrophages by 4-Hydroxynonenal, a Product of Oxidized Omega-6 Fatty Acids Am. J. Pathol., October 1, 2008; 173(4): 1057 - 1066. [Abstract] [Full Text] [PDF]

				Y. Koike, T. Hisada, M. Utsugi, T. Ishizuka, Y. Shimizu, A. Ono, Y. Murata, J. Hamuro, M. Mori, and K. Dobashi Glutathione Redox Regulates Airway Hyperresponsiveness and Airway Inflammation in Mice Am. J. Respir. Cell Mol. Biol., September 1, 2007; 37(3): 322 - 329. [Abstract] [Full Text] [PDF]

				M. Utsugi, K. Dobashi, T. Ishizuka, T. Kawata, T. Hisada, Y. Shimizu, A. Ono, and M. Mori Rac1 Negatively Regulates Lipopolysaccharide-Induced IL-23 p19 Expression in Human Macrophages and Dendritic Cells and NF-{kappa}B p65 trans Activation Plays a Novel Role J. Immunol., October 1, 2006; 177(7): 4550 - 4557. [Abstract] [Full Text] [PDF]

				Z. Lin, D. K. Crockett, S. D. Jenson, M. S. Lim, and K. S. J. Elenitoba-Johnson Quantitative Proteomic and Transcriptional Analysis of the Response to the p38 Mitogen-activated Protein Kinase Inhibitor SB203580 in Transformed Follicular Lymphoma Cells Mol. Cell. Proteomics, August 1, 2004; 3(8): 820 - 833. [Abstract] [Full Text] [PDF]

				J. Yamada, K. Maruyama, Y. Sano, S. Kinoshita, Y. Murata, and J. Hamuro Promotion of Corneal Allograft Survival by the Induction of Oxidative Macrophages Invest. Ophthalmol. Vis. Sci., February 1, 2004; 45(2): 448 - 454. [Abstract] [Full Text] [PDF]

				W. Ma, K. Gee, W. Lim, K. Chambers, J. B. Angel, M. Kozlowski, and A. Kumar Dexamethasone Inhibits IL-12p40 Production in Lipopolysaccharide-Stimulated Human Monocytic Cells by Down-Regulating the Activity of c-Jun N-Terminal Kinase, the Activation Protein-1, and NF-{kappa}B Transcription Factors J. Immunol., January 1, 2004; 172(1): 318 - 330. [Abstract] [Full Text] [PDF]

				M. Utsugi, K. Dobashi, T. Ishizuka, K. Endou, J. Hamuro, Y. Murata, T. Nakazawa, and M. Mori c-Jun N-Terminal Kinase Negatively Regulates Lipopolysaccharide-Induced IL-12 Production in Human Macrophages: Role of Mitogen-Activated Protein Kinase in Glutathione Redox Regulation of IL-12 Production J. Immunol., July 15, 2003; 171(2): 628 - 635. [Abstract] [Full Text] [PDF]

				M. Utsugi, K. Dobashi, T. Ishizuka, K. Masubuchi, Y. Shimizu, T. Nakazawa, and M. Mori C-Jun-NH2-Terminal Kinase Mediates Expression of Connective Tissue Growth Factor Induced by Transforming Growth Factor-{beta}1 in Human Lung Fibroblasts Am. J. Respir. Cell Mol. Biol., June 1, 2003; 28(6): 754 - 761. [Abstract] [Full Text] [PDF]

				Y. Murata, A. Yamashita, T. Saito, K. Sugamura, and J. Hamuro The conversion of redox status of peritoneal macrophages during pathological progression of spontaneous inflammatory bowel disease in Janus family tyrosine kinase 3-/- and IL-2 receptor {gamma}-/- mice Int. Immunol., June 1, 2002; 14(6): 627 - 636. [Abstract] [Full Text] [PDF]