title: Inflammatory Cytokines Contribute to Asbestos-Induced Injury of Mesothelial Cells.
abstract: BACKGROUND
  Several diseases have been related to asbestos exposure, including the pleural tumor mesothelioma. The mechanism of pleural injury by asbestos fibers is not yet fully understood. The inflammatory response with release of mediators leading to a dysregulation of apoptosis may play a pivotal role in the pathophysiology of asbestos-induced pleural disease.
  
  
  OBJECTIVE
  To determine whether pro-inflammatory cytokines produced by asbestos-exposed pleural mesothelial cells modify the injury induced by the asbestos.
  
  
  METHODS
  Mouse pleural mesothelial cells (PMC) were exposed to crocidolite or chrysotile asbestos fibers (3.0 μg/cm(2)) for 4, 24, or 48 h and assessed for viability, necrosis and apoptosis, and the production of cytokines IL-1β, IL-6 and macrophage inflammatory protein-2 (MIP-2). Cells exposed to fibers were also treated with antibodies anti-IL-1β, anti-IL-6, anti- IL-1β+anti-IL-6 or anti-MIP-2 or their irrelevant isotypes, and assessed for apoptosis and necrosis. Non-exposed cells and cells treated with wollastonite, an inert particle, were used as controls.
  
  
  RESULTS
  Mesothelial cells exposed to either crocidolite or chrysotile underwent both apoptosis and necrosis and released cytokines IL-1β, IL-6 and MIP-2. In the crocidolite group, apoptosis and the levels of all cytokines were higher than in the chrysotile group, at comparable concentrations. Neutralization of IL-1β andIL-6, but not MIP-2, inhibited apoptosis and necrosis, especially in the cells exposed to crocidolite fibers.
  
  
  CONCLUSIONS
  Both crocidolite and chrysotile asbestos fibers induced apoptosis and produced an acute inflammatory response characterized by elevated levels of IL-1β, IL-6 and MIP-2 in cultured mouse PMC. IL-1β and IL-6, but not MIP-2, were shown to contribute to asbestos-induced injury, especially in the crocidolite group.
authors.affiliation: Pleura Laboratory, Pulmonary Division - Heart Institute (InCor), University of São Paulo Medical School, Rua Dr. Eneas Carvalho Aguiar 44, 10 andar, Cerqueira Cesar, São Paulo, 05403-000, Brazil. milena.acencio@incor.usp.br.
authors.forename: Milena Marques Pagliarelli
authors.initials: MM
authors.lastname: Acencio
authors.affiliation: Pleura Laboratory, Pulmonary Division - Heart Institute (InCor), University of São Paulo Medical School, Rua Dr. Eneas Carvalho Aguiar 44, 10 andar, Cerqueira Cesar, São Paulo, 05403-000, Brazil.
authors.forename: Barbara
authors.initials: B
authors.lastname: Soares
authors.affiliation: Pleura Laboratory, Pulmonary Division - Heart Institute (InCor), University of São Paulo Medical School, Rua Dr. Eneas Carvalho Aguiar 44, 10 andar, Cerqueira Cesar, São Paulo, 05403-000, Brazil.|Medical College of Jundiai, São Paulo, Brazil.
authors.forename: Evaldo
authors.initials: E
authors.lastname: Marchi
authors.affiliation: Pleura Laboratory, Pulmonary Division - Heart Institute (InCor), University of São Paulo Medical School, Rua Dr. Eneas Carvalho Aguiar 44, 10 andar, Cerqueira Cesar, São Paulo, 05403-000, Brazil.
authors.forename: Carlos Sergio Rocha
authors.initials: CS
authors.lastname: Silva
authors.affiliation: Pleura Laboratory, Pulmonary Division - Heart Institute (InCor), University of São Paulo Medical School, Rua Dr. Eneas Carvalho Aguiar 44, 10 andar, Cerqueira Cesar, São Paulo, 05403-000, Brazil.
authors.forename: Lisete Ribeiro
authors.initials: LR
authors.lastname: Teixeira
authors.affiliation: Lung Biology Center, UCSF, San Francisco, CA, USA.
authors.forename: V C
authors.initials: VC
authors.lastname: Broaddus
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D017638:Asbestos, Crocidolite / Q000633:toxicity*; D017632:Asbestos, Serpentine / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D054426:Chemokine CXCL2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D009336:Necrosis / Q000139:chemically induced; D010994:Pleura / Q000166:cytology; D000093242:Interleukin-6 Inhibitors
chemical_list: D017638:Asbestos, Crocidolite; D017632:Asbestos, Serpentine; D054426:Chemokine CXCL2; D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D000093242:Interleukin-6 Inhibitors
keywords: Apoptosis; Asbestos; Cytokines; Inflammation mediators; Mesothelioma