title: Inhibition of cyclooxygenase-1 and cyclooxygenase-2 impairs Trypanosoma cruzi entry into cardiac cells and promotes differential modulation of the inflammatory response.
abstract: The intracellular protozoan parasite Trypanosoma cruzi is the etiologic agent of Chagas disease, a serious disorder that affects millions of people in Latin America. Cell invasion by T. cruzi and its intracellular replication are essential to the parasite's life cycle and for the development of Chagas disease. Here, we present evidence suggesting the involvement of the host's cyclooxygenase (COX) enzymes during T. cruzi invasion. Pharmacological antagonists for COX-1 (aspirin) and COX-2 (celecoxib) caused marked inhibition of T. cruzi infection when rat cardiac cells were pretreated with these nonsteroidal anti-inflammatory drugs (NSAIDs) for 60 min at 37°C before inoculation. This inhibition was associated with an increase in the production of NO and interleukin-1β and decreased production of transforming growth factor β (TGF-β) by cells. Taken together, these results indicate that COX-1 more than COX-2 is involved in the regulation of anti-T. cruzi activity in cardiac cells, and they provide a better understanding of the influence of TGF-β-interfering therapies on the innate inflammatory response to T. cruzi infection and may represent a very pertinent target for new therapeutic treatments of Chagas disease.
authors.affiliation: Laboratório de Imunopatologia Experimental, Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina, Paraná, Brazil.
authors.forename: Aparecida D
authors.initials: AD
authors.lastname: Malvezi
authors.affiliation: Laboratório de Patofisiologia e Radicais Livres, Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina, Paraná, Brazil.
authors.forename: Carolina
authors.initials: C
authors.lastname: Panis
authors.affiliation: Laboratório de Imunopatologia Experimental, Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina, Paraná, Brazil.
authors.forename: Rosiane V
authors.initials: RV
authors.lastname: da Silva
authors.affiliation: Laboratório de Imunopatologia Experimental, Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina, Paraná, Brazil.
authors.forename: Rafael Carvalho
authors.initials: RC
authors.lastname: de Freitas
authors.affiliation: Laboratório de Imunopatologia Experimental, Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina, Paraná, Brazil.
authors.forename: Maria I
authors.initials: MI
authors.lastname: Lovo-Martins
authors.affiliation: Laboratório de Imunopatologia Experimental, Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina, Paraná, Brazil.
authors.forename: Vera L H
authors.initials: VL
authors.lastname: Tatakihara
authors.affiliation: Laboratório de Imunopatologia Experimental, Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina, Paraná, Brazil.
authors.forename: Nágela G
authors.initials: NG
authors.lastname: Zanluqui
authors.affiliation: Laboratório de Immunologia, Instituto do Coração, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Edecio Cunha
authors.initials: EC
authors.lastname: Neto
authors.affiliation: Instituto Carlos Chagas/Fiocruz, Curitiba, Brazil.
authors.forename: Samuel
authors.initials: S
authors.lastname: Goldenberg
authors.affiliation: Instituto Carlos Chagas/Fiocruz, Curitiba, Brazil.
authors.forename: Juliano
authors.initials: J
authors.lastname: Bordignon
authors.affiliation: Laboratório de Biologia Molecular de Microrganismos, Departamento de Microbiologia, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina, Paraná, Brazil.
authors.forename: Sueli F
authors.initials: SF
authors.lastname: Yamada-Ogatta
authors.affiliation: Departamento de Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina, Paraná, Brazil.
authors.forename: Marli C
authors.initials: MC
authors.lastname: Martins-Pinge
authors.affiliation: Laboratório de Patofisiologia e Radicais Livres, Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina, Paraná, Brazil.
authors.forename: Rubens
authors.initials: R
authors.lastname: Cecchini
authors.affiliation: Laboratório de Imunopatologia Experimental, Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina, Paraná, Brazil pingefilho@uel.br.
authors.forename: Phileno
authors.initials: P
authors.lastname: Pinge-Filho
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D000068579:Celecoxib; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D051545:Cyclooxygenase 1 / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D007113:Immunity, Innate / Q000187:drug effects; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000378:metabolism; D032386:Myoblasts, Cardiac / Q000469:parasitology*; D009569:Nitric Oxide / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D013449:Sulfonamides / Q000494:pharmacology; D016211:Transforming Growth Factor alpha / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014349:Trypanosoma cruzi / Q000187:drug effects / Q000276:immunology* / Q000472:pathogenicity*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D053583:Interleukin-1beta; D011720:Pyrazoles; D013449:Sulfonamides; D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta; D009569:Nitric Oxide; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D000068579:Celecoxib; D001241:Aspirin
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