title: Natural haemozoin induces expression and release of human monocyte tissue inhibitor of metalloproteinase-1.
abstract: Recently matrix metalloproteinase-9 (MMP-9) and its endogenous inhibitor (tissue inhibitor of metalloproteinase-1, TIMP-1) have been implicated in complicated malaria. In vivo, mice with cerebral malaria (CM) display high levels of both MMP-9 and TIMP-1, and in human patients TIMP-1 serum levels directly correlate with disease severity. In vitro, natural haemozoin (nHZ, malarial pigment) enhances monocyte MMP-9 expression and release. The present study analyses the effects of nHZ on TIMP-1 regulation in human adherent monocytes. nHZ induced TIMP-1 mRNA expression and protein release, and promoted TNF-α, IL-1β, and MIP-1α/CCL3 production. Blocking antibodies or recombinant cytokines abrogated or mimicked nHZ effects on TIMP-1, respectively. p38 MAPK and NF-κB inhibitors blocked all nHZ effects on TIMP-1 and pro-inflammatory molecules. Still, total gelatinolytic activity was enhanced by nHZ despite TIMP-1 induction. Collectively, these data indicate that nHZ induces inflammation-mediated expression and release of human monocyte TIMP-1 through p38 MAPK- and NF-κB-dependent mechanisms. However, TIMP-1 induction is not sufficient to counterbalance nHZ-dependent MMP-9 enhancement. Future investigation on proteinase-independent functions of TIMP-1 (i.e. cell survival promotion and growth/differentiation inhibition) is needed to clarify the role of TIMP-1 in malaria pathogenesis.
authors: Dipartimento di Oncologia, Università di Torino, Torino, Italy.
authors: Manuela
authors: M
authors: Polimeni
authors: Elena
authors: E
authors: Valente
authors: Daniela
authors: D
authors: Ulliers
authors: Ghislain
authors: G
authors: Opdenakker
authors: Philippe E
authors: PE
authors: Van den Steen
authors: Giuliana
authors: G
authors: Giribaldi
authors: Mauro
authors: M
authors: Prato
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D005786:Gene Expression Regulation / Q000187:drug effects*; D006420:Hemeproteins / Q000494:pharmacology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012995:Solubility; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics* / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D006420:Hemeproteins; D016328:NF-kappa B; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; C020753:hemozoin; D048051:p38 Mitogen-Activated Protein Kinases; D020780:Matrix Metalloproteinase 9
references: Curr Top Med Chem. 2011;11(10):1226-54
references: 21401508
references: Cell Microbiol. 2011 Aug;13(8):1275-85
references: 21707906
references: FEBS Lett. 2003 Sep 25;552(2-3):141-4
references: 14527676
references: PLoS One. 2012;7(6):e39497
references: 22724024
references: J Infect Dis. 2009 May 15;199(10):1536-45
references: 19392627
references: J Immunol. 2006 Nov 1;177(9):6344-52
references: 17056565
references: Dis Markers. 2011;31(6):327-35
references: 22182805
references: J Immunol. 2005 Jan 1;174(1):475-84
references: 15611273
references: Infect Immun. 2006 Oct;74(10):5561-73
references: 16988231
references: World J Biol Chem. 2011 Jan 26;2(1):14-24
references: 21537473
references: Int J Parasitol. 2010 Aug 1;40(9):1003-12
references: 20211185
references: Cancer Metastasis Rev. 2006 Mar;25(1):99-113
references: 16680576
references: Clin Vaccine Immunol. 2006 Mar;13(3):319-28
references: 16522772
references: Lab Invest. 2006 Sep;86(9):873-88
references: 16865090
references: J Immunol. 1997 Mar 1;158(5):2327-33
references: 9036981
references: J Clin Invest. 1998 Dec 1;102(11):2002-10
references: 9835626
references: J Immunol. 2005 Nov 15;175(10):6436-42
references: 16272296
references: Cardiovasc Res. 2006 Feb 15;69(3):562-73
references: 16405877
references: Brain. 2003 Dec;126(Pt 12):2738-49
references: 14506071
references: Asian Pac J Trop Med. 2011 Dec;4(12):925-30
references: 22118025
references: J Infect Dis. 2008 Jun 1;197(11):1614-20
references: 18700258
references: Placenta. 2011 Aug;32(8):579-85
references: 21632106
references: J Immunol. 1998 Sep 15;161(6):3071-6
references: 9743373
references: Curr Pharm Des. 2012;18(25):3645-8
references: 22574977
references: Am J Respir Cell Mol Biol. 2013 May;48(5):589-600
references: 23328641
references: Immunopharmacology. 2000 May;47(2-3):185-201
references: 10878289
references: Expert Rev Anti Infect Ther. 2011 Sep;9(9):803-19
references: 21905788
references: Crit Rev Biochem Mol Biol. 2007 May-Jun;42(3):113-85
references: 17562450
references: J Biol Chem. 2009 Jun 5;284(23):15750-61
references: 19359247
references: J Biol Chem. 2006 Jul 7;281(27):18626-37
references: 16672230
references: J Biol Chem. 2001 Oct 26;276(43):39713-20
references: 11500489
references: J Immunol. 2009 Oct 15;183(8):5208-20
references: 19783673
references: Lymphokine Cytokine Res. 1991 Aug;10(4):317-24
references: 1932376
references: Blood. 2003 Jan 15;101(2):722-8
references: 12393662
references: Biofactors. 2013 May-Jun;39(3):304-14
references: 23355332
references: Proc Natl Acad Sci U S A. 2012 Feb 7;109(6):E309-16
references: 22223664
references: J Exp Med. 1992 Oct 1;176(4):1033-41
references: 1402649
references: J Immunol. 2000 Jun 15;164(12):6174-9
references: 10843667
references: Malar J. 2008 Feb 29;7:42
references: 18312657
references: Infect Immun. 2010 Nov;78(11):4912-21
references: 20732999
references: Asian Pac J Trop Med. 2013 Mar;6(3):195-9
references: 23375032
references: J Trop Med. 2011;2011:628435
references: 21760809
references: Biochemistry. 2008 Feb 26;47(8):2689-99
references: 18237197
references: Am J Physiol Heart Circ Physiol. 2007 Sep;293(3):H1590-5
references: 17545477
references: EMBO J. 2006 Sep 6;25(17):3934-42
references: 16917503
references: FEBS Lett. 1991 Jun 17;284(1):73-8
references: 1647974
references: Nucleic Acids Res. 2001 May 1;29(9):e45
references: 11328886
references: J Rheumatol. 2001 Apr;28(4):712-8
references: 11327240
references: Asian Pac J Trop Med. 2011 Sep;4(9):756
references: 21967702
references: Malar J. 2012 Jun 10;11:191
references: 22682094
references: J Immunol. 2003 Oct 15;171(8):4243-53
references: 14530348
references: Immunol Lett. 2006 Jul 15;106(1):34-41
references: 16720051
references: Infect Immun. 2013 Jun;81(6):1889-904
references: 23509137
references: J Ethnopharmacol. 1986 Feb;15(2):201-9
references: 3520157
references: Cell Biochem Funct. 2014 Jan;32(1):5-15
references: 23468369
references: J Biol Chem. 1999 Jul 30;274(31):21491-4
references: 10419448
references: Sci Signal. 2008 Jul 08;1(27):re6
references: 18612141
references: Pharmacol Ther. 2012 Mar;133(3):257-79
references: 22138604
references: Cell Microbiol. 2010 Dec;12(12):1780-91
references: 20678173
references: Exp Cell Res. 2009 May 15;315(9):1584-92
references: 18930046
references: Biochim Biophys Acta. 2010 Jan;1803(1):55-71
references: 20080133
references: J Biol. 2006;5(2):4
references: 16620370
references: Malar J. 2008 Aug 18;7:157
references: 18710562
references: Chem Res Toxicol. 2009 Mar 16;22(3):433-45
references: 19191707
references: Biochem J. 1993 Dec 15;296 ( Pt 3):803-9
references: 8280080
references: Microbes Infect. 2009 Jul-Aug;11(8-9):811-9
references: 19427395
references: Haematologica. 2004 Apr;89(4):492-3
references: 15075084
references: Malar J. 2010 Jul 19;9:208
references: 20642847
references: Cancer Res. 1999 Dec 15;59(24):6267-75
references: 10626822
references: J Neurovirol. 2007;13(1):2-10
references: 17454443