title: Mycoplasma fermentans MALP-2 induces heme oxygenase-1 expression via mitogen-activated protein kinases and Nrf2 pathways to modulate cyclooxygenase 2 expression in human monocytes.
abstract: Heme oxygenase-1 (HO-1) is a stress-inducible rate-limiting enzyme in heme degradation that confers cytoprotection against oxidative injury and performs a vital function in the maintenance of cell hemostasis. Increasing numbers of reports have indicated that mycoplasma-derived membrane lipoproteins/lipopeptides, such as macrophage-activating lipopeptide-2 (MALP-2), function as agents that stimulate the immune system by producing various inflammatory mediators, such as cytokines and cyclooxygenase 2 (COX-2), which play roles in the pathogenesis of inflammatory responses during mycoplasma infection. Here, we report that MALP-2 induced HO-1 mRNA and protein expression and upregulated HO-1 enzyme activity in THP-1 cells. Specific inhibitors of mitogen-activated protein kinases (MAPKs), SB203580, PD98059, and SP600125, significantly abolished HO-1 expression. In addition, MALP-2 also induced NF-E2-related factor 2 (Nrf2) translocation, and the silencing of Nrf2 expression in THP-1 cells decreased the levels of MALP-2-mediated HO-1 expression. Furthermore, COX-2 protein expression levels were upregulated in THP-1 cells in response to MALP-2, and transfection with small interfering RNAs of HO-1 significantly increased COX-2 accumulation. These results demonstrate that MALP-2 induces HO-1 expression via MAPKs and Nrf2 pathways and, furthermore, that MALP-2-induced COX-2 expression was modulated by HO-1 in THP-1 cells.
authors.affiliation: Institution of Pathogenic Biology, Medical College, University of South China, Hengyang, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Ma
authors.forename: Xiaoxing
authors.initials: X
authors.lastname: You
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Zeng
authors.forename: Jun
authors.initials: J
authors.lastname: He
authors.forename: Liangzhuan
authors.initials: L
authors.lastname: Liu
authors.forename: Zhongliang
authors.initials: Z
authors.lastname: Deng
authors.forename: Chuanhao
authors.initials: C
authors.lastname: Jiang
authors.forename: Haiying
authors.initials: H
authors.lastname: Wu
authors.forename: Cuiming
authors.initials: C
authors.lastname: Zhu
authors.forename: Minjun
authors.initials: M
authors.lastname: Yu
authors.forename: Yimou
authors.initials: Y
authors.lastname: Wu
mesh_terms: D001426:Bacterial Proteins / Q000276:immunology; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D005786:Gene Expression Regulation; D051547:Heme Oxygenase-1 / Q000096:biosynthesis*; D006801:Humans; D055666:Lipopeptides / Q000276:immunology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009000:Monocytes / Q000276:immunology*; D016858:Mycoplasma fermentans / Q000276:immunology*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D001426:Bacterial Proteins; D055666:Lipopeptides; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; C106335:macrophage stimulatory lipopeptide 2; D051547:Heme Oxygenase-1; D051546:Cyclooxygenase 2; D020928:Mitogen-Activated Protein Kinases
references.citation: Am J Respir Cell Mol Biol. 2009 Apr;40(4):474-81
references.pmid: 18931326
references.citation: Biochem Pharmacol. 2004 Aug 1;68(3):417-21
references.pmid: 15242808
references.citation: J Signal Transduct. 2012;2012:463617
references.pmid: 22523682
references.citation: J Immunol. 2004 Aug 15;173(4):2683-91
references.pmid: 15294986
references.citation: Arterioscler Thromb Vasc Biol. 2013 Sep;33(9):2097-104
references.pmid: 23868938
references.citation: Eur J Immunol. 2004 Mar;34(3):899-907
references.pmid: 14991620
references.citation: Biochim Biophys Acta. 2011 Sep;1813(9):1619-33
references.pmid: 21167873
references.citation: Biochem J. 2000 Oct 1;351(Pt 1):95-105
references.pmid: 10998351
references.citation: Am J Physiol Lung Cell Mol Physiol. 2010 Jun;298(6):L870-9
references.pmid: 20348279
references.citation: Free Radic Biol Med. 2004 May 15;36(10):1199-207
references.pmid: 15110384
references.citation: J Huazhong Univ Sci Technolog Med Sci. 2012 Oct;32(5):737-745
references.pmid: 23073806
references.citation: Expert Opin Ther Targets. 2012 Jun;16(6):527-40
references.pmid: 22519838
references.citation: J Biol Chem. 1998 Dec 18;273(51):34391-8
references.pmid: 9852105
references.citation: J Clin Invest. 2006 Apr;116(4):984-95
references.pmid: 16585964
references.citation: J Clin Invest. 2008 Jan;118(1):239-47
references.pmid: 18060048
references.citation: J Immunol. 2005 Oct 1;175(7):4408-15
references.pmid: 16177082
references.citation: FASEB J. 2012 Jul;26(7):2911-8
references.pmid: 22490782
references.citation: Infect Immun. 2008 Jan;76(1):270-7
references.pmid: 17954722
references.citation: Am J Physiol. 1999 May;276(5):H1493-501
references.pmid: 10330231
references.citation: J Biol Chem. 2003 Nov 7;278(45):44675-82
references.pmid: 12947090
references.citation: Lung Cancer. 2006 Mar;51(3):283-96
references.pmid: 16376453
references.citation: J Reprod Immunol. 2006 Dec;72(1-2):46-59
references.pmid: 16600383
references.citation: Infect Immun. 2003 Aug;71(8):4456-62
references.pmid: 12874325
references.citation: Am J Physiol Lung Cell Mol Physiol. 2010 Feb;298(2):L261-9
references.pmid: 19897740
references.citation: Curr Drug Targets. 2010 Dec;11(12):1532-40
references.pmid: 20704548
references.citation: Neuro Oncol. 2012 Nov;14(11):1367-78
references.pmid: 23074199
references.citation: Exp Dermatol. 2004 Dec;13(12):731-9
references.pmid: 15560756
references.citation: J Immunol. 2008 Nov 15;181(10):6730-7
references.pmid: 18981090
references.citation: Antioxid Redox Signal. 2007 Dec;9(12):2157-73
references.pmid: 17845132
references.citation: Mediators Inflamm. 2008;2008:195427
references.pmid: 18464921
references.citation: Trends Mol Med. 2009 Feb;15(2):50-8
references.pmid: 19162549
references.citation: Chem Biol Interact. 2010 Dec 5;188(3):437-45
references.pmid: 20833156
references.citation: J Neuroinflammation. 2010 Nov 30;7:86
references.pmid: 21118574
references.citation: Mol Cell Biochem. 2011 Sep;355(1-2):109-15
references.pmid: 21533649
references.citation: J Immunol. 2009 Mar 15;182(6):3809-18
references.pmid: 19265160
references.citation: Am J Respir Cell Mol Biol. 2009 Sep;41(3):251-60
references.pmid: 19617398
references.citation: Immune Netw. 2009 Feb;9(1):12-9
references.pmid: 20107533
references.citation: Am J Physiol Renal Physiol. 2006 Mar;290(3):F563-71
references.pmid: 16461755
references.citation: J Immunol. 2008 Oct 1;181(7):5098-110
references.pmid: 18802114
references.citation: Toxicol Sci. 2009 Jan;107(1):227-37
references.pmid: 18832182
references.citation: J Periodontol. 2009 Dec;80(12):2045-55
references.pmid: 19961388
references.citation: Am J Physiol Lung Cell Mol Physiol. 2005 Dec;289(6):L1131-7
references.pmid: 16155084
references.citation: Biochim Biophys Acta. 2013 Jan;1830(1):2214-25
references.pmid: 23046979
references.citation: J Biol Chem. 2011 Mar 11;286(10):7841-7853
references.pmid: 21205826
references.citation: Blood. 2010 Mar 25;115(12):2543-52
references.pmid: 20056792
references.citation: Infect Immun. 1999 Dec;67(12):6303-8
references.pmid: 10569741
references.citation: Eur J Immunol. 2010 May;40(5):1272-83
references.pmid: 20213735
references.citation: Toxicol Appl Pharmacol. 2010 Sep 1;247(2):146-57
references.pmid: 20600219
references.citation: Chem Biol Interact. 2011 Apr 25;190(2-3):129-38
references.pmid: 21315065