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Blood, 15 February 2006, Vol. 107, No. 4, pp. 1513-1520. Prepublished online as a Blood First Edition Paper on October 25, 2005; DOI 10.1182/blood-2005-04-1707. This Article Full Text (PDF) All Versions of this Article: 2005-04-1707v1 107/4/1513    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Khan, N. Articles by Mukhopadhyay, S. Search for Related Content PubMed PubMed Citation Articles by Khan, N. Articles by Mukhopadhyay, S. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 27, 2005 Accepted October 10, 2005 Hydrogen peroxide inhibits IL-12 p40 induction in macrophages by inhibiting c-rel translocation to the nucleus through activation of calmodulin protein Nooruddin Khan, Sheikh S Rahim, Chandra S Boddupalli, Sheikh Ghousunnissa, S Padma, Niteen Pathak, Dorairajan Thiagarajan, Seyed E Hasnain, and Sangita Mukhopadhyay* Laboratory of Molecular and Cellular Biology, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, Andhra Pradesh, India Research and Development, Indian Immunologicals Ltd, Hyderabad, Andhra Pradesh, India Laboratory of Molecular and Cellular Biology, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, Andhra Pradesh, India; Jawaharlal Nehru Center for Advanced Scientific Research, Bangalore, India * Corresponding author; email: sangita{at}cdfd.org.in. Although the antimicrobial activity of reactive oxygen species (ROS) is well defined, the role of ROS regulating immune response of the body is not well understood. We now provide evidence that hydrogen peroxide (H2O2), a major component of ROS, inhibits interleukin-12 (IL-12) p40 and IL-12 p70 induction in murine macrophages and catalase pre-treatment prevents H2O2-mediated down-regulation of IL-12. Endogenous accumulation of H2O2/ROS in macrophages treated with alloxan resulted in IL-12 p40 inhibition. Though nuclear expression of both p50 and p65 NF-kappaB increased upon H2O2 exposure, nuclear c-rel level was inhibited. Over-expression of c-rel restored IL-12 p40 upon stimulation with LPS+IFN-gamma during H2O2 treatment. H2O2 did not inhibit c-rel induction in cytosol, however, it prevented the transport of c-rel from cytosol to nucleus. H2O2 activated calmodulin (CaM) protein in the cytosol which subsequently sequestered c-rel in the cytosol preventing its transport to the nucleus. The CaM inhibitor trifIuoperazine increased both nuclear c-rel and IL-12 p40 levels in H2O2-treated macrophages, emphasizing a role of CaM in these processes. H2O2/ROS thus downregulates IL-12 induction in macrophages by a novel pathway inhibiting c-rel translocation to the nucleus through activation of CaM protein. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Nair, P. A. Ramaswamy, S. Ghosh, D. C. Joshi, N. Pathak, I. Siddiqui, P. Sharma, S. E. Hasnain, S. C. Mande, and S. Mukhopadhyay The PPE18 of Mycobacterium tuberculosis Interacts with TLR2 and Activates IL-10 Induction in Macrophage J. Immunol., November 15, 2009; 183(10): 6269 - 6281. [Abstract] [Full Text] [PDF] P. R. Kroening, T. W. Barnes, L. Pease, A. Limper, H. Kita, and R. Vassallo Cigarette Smoke-Induced Oxidative Stress Suppresses Generation of Dendritic Cell IL-12 and IL-23 through ERK-Dependent Pathways J. Immunol., July 15, 2008; 181(2): 1536 - 1547. [Abstract] [Full Text] [PDF] D. I. Kasahara, M. E. Poynter, Z. Othman, D. Hemenway, and A. van der Vliet Acrolein Inhalation Suppresses Lipopolysaccharide-Induced Inflammatory Cytokine Production but Does Not Affect Acute Airways Neutrophilia J. Immunol., July 1, 2008; 181(1): 736 - 745. [Abstract] [Full Text] [PDF] N. Khan, K. Alam, S. Nair, V. L. Valluri, K. J. R. Murthy, and S. Mukhopadhyay Association of Strong Immune Responses to PPE Protein Rv1168c with Active Tuberculosis Clin. Vaccine Immunol., June 1, 2008; 15(6): 974 - 980. [Abstract] [Full Text] [PDF] N. Khan, S. Ghousunnissa, S. M. Jegadeeswaran, D. Thiagarajan, S. E. Hasnain, and S. Mukhopadhyay Anti-B7-1/B7-2 antibody elicits innate-effector responses in macrophages through NF-{kappa}B-dependent pathway Int. Immunol., April 1, 2007; 19(4): 477 - 486. [Abstract] [Full Text] [PDF]

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