title: Production of MMP-9 and inflammatory cytokines by Trypanosoma cruzi-infected macrophages.
abstract: Matrix metalloproteinases (MMPs) constitute a large family of Zn(2+) and Ca(2+) dependent endopeptidases implicated in tissue remodeling and chronic inflammation. MMPs also play key roles in the activation of growth factors, chemokines and cytokines produced by many cell types, including lymphocytes, granulocytes, and, in particular, activated macrophages. Their synthesis and secretion appear to be important in a number of physiological processes, including the inflammatory process. Here, we investigated the interaction between human and mouse macrophages with T. cruzi Colombian and Y strains to characterize MMP-9 and cytokine production in this system. Supernatants and total extract of T. cruzi infected human and mouse macrophages were obtained and used to assess MMP-9 profile and inflammatory cytokines. The presence of metalloproteinase activity was determined by zymography, enzyme-linked immunosorbent assay and immunoblotting assays. The effect of cytokines on MMP-9 production in human macrophages was verified by previous incubation of cytokines on these cells in culture, and analyzed by zymography. We detected an increase in MMP-9 production in the culture supernatants of T. cruzi infected human and mouse macrophages. The addition of IL-1β or TNF-α to human macrophage cultures increased MMP-9 production. In contrast, MMP-9 production was down-modulated when human macrophage cultures were treated with IFN-γ or IL-4 before infection. Human macrophages infected with T. cruzi Y or Colombian strains produced increased levels of MMP-9, which was related to the production of cytokines such as IL-1β, TNF-α and IL-6.
authors.affiliation: Laboratório de Imunologia Clínica, Av. Brasil 4365 - Manguinhos, Rio de Janeiro, CEP 21040-360, Brasil. Electronic address: rospinho@ioc.fiocruz.br.
authors.forename: Rosa Teixeira
authors.initials: RT
authors.lastname: de Pinho
authors.affiliation: Laboratório de Imunologia Clínica, Av. Brasil 4365 - Manguinhos, Rio de Janeiro, CEP 21040-360, Brasil; Fundação Ataulpho de Paiva, Av. Pedro II 260 - São Cristóvão, Rio de Janeiro, CEP 2094 1000, Brasil.
authors.forename: Wellington Seguins
authors.initials: WS
authors.lastname: da Silva
authors.affiliation: Laboratório de Biologia Molecular e Doenças Endêmicas- IOC - FIOCRUZ, Av. Brasil 4365 - Manguinhos, Rio de Janeiro, CEP 21040-360, Brasil.
authors.forename: Luzia Monteiro
authors.initials: LM
authors.lastname: de Castro Côrtes
authors.affiliation: Laboratório de Imunologia Clínica, Av. Brasil 4365 - Manguinhos, Rio de Janeiro, CEP 21040-360, Brasil.
authors.forename: Periela
authors.initials: P
authors.lastname: da Silva Vasconcelos Sousa
authors.affiliation: Laboratório de Biologia Molecular e Doenças Endêmicas- IOC - FIOCRUZ, Av. Brasil 4365 - Manguinhos, Rio de Janeiro, CEP 21040-360, Brasil; Laboratório de Bioquímica de Tripanosomatídeos - IOC - FIOCRUZ, Av. Brasil 4365 - Manguinhos, Rio de Janeiro, CEP 21040-360, Brasil.
authors.forename: Renata Oliveira
authors.initials: RO
authors.lastname: de Araujo Soares
authors.affiliation: Laboratório de Biologia Molecular e Doenças Endêmicas- IOC - FIOCRUZ, Av. Brasil 4365 - Manguinhos, Rio de Janeiro, CEP 21040-360, Brasil.
authors.forename: Carlos Roberto
authors.initials: CR
authors.lastname: Alves
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D014355:Chagas Disease / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008264:Macrophages / Q000201:enzymology / Q000276:immunology / Q000469:parasitology*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000378:metabolism; D051379:Mice; D009000:Monocytes / Q000166:cytology; D014349:Trypanosoma cruzi / Q000276:immunology / Q000502:physiology*
chemical_list: D016207:Cytokines; D020780:Matrix Metalloproteinase 9
keywords: Colombian strain; IFN-γ; IL-1β; IL-4; IL-6; THP-1 macrophages; TNF-α; Trypanosoma cruzi; Y strain; cytokines; human macrophages; matrix metalloproteinase-9; mouse macrophages