RESUMO
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-1ß, IL-6 and macrophage inflammatory protein-2 (MIP-2). Cells exposed to fibers were also treated with antibodies anti-IL-1ß, anti-IL-6, anti- IL-1ß+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-1ß, 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-1ß 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-1ß, IL-6 and MIP-2 in cultured mouse PMC. IL-1ß and IL-6, but not MIP-2, were shown to contribute to asbestos-induced injury, especially in the crocidolite group.
Assuntos
Asbesto Crocidolita/toxicidade , Asbestos Serpentinas/toxicidade , Citocinas/metabolismo , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Animais , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Quimiocina CXCL2/antagonistas & inibidores , Quimiocina CXCL2/metabolismo , Citocinas/antagonistas & inibidores , Células Epiteliais/efeitos dos fármacos , Interleucina-1beta/antagonistas & inibidores , Interleucina-1beta/metabolismo , Interleucina-6/antagonistas & inibidores , Interleucina-6/metabolismo , Camundongos , Necrose/induzido quimicamente , Pleura/citologiaRESUMO
Inflammatory processes are a major cause of pleural effusion. Besides being important clinically for diagnosis and treatment of patients with pleural effusions, studies of inflammatory pleural effusions shed light on the mechanisms of pleural liquid formation and also on general mechanisms of inflammation. In this current review, we have chosen papers within the past year that highlight aspects of clinical and research interest concerning inflammation and inflammatory pleural effusions. In some studies, investigators have investigated basic mechanisms of the roles of cytokines and adhesion molecules in inflammatory cell recruitment and leakage of liquid. In other studies, clinicians have attempted to measure inflammatory markers as a means of diagnosis. In light of these studies, we discuss the current understanding of inflammatory pleural effusions and suggest future avenues for exploration.