title: NLRP3 promotes inflammation-induced skin cancer but is dispensable for asbestos-induced mesothelioma.
abstract: Asbestos exposure can result in serious and frequently lethal diseases, including malignant mesothelioma. The host sensor for asbestos-induced inflammation is the NLRP3 inflammasome and it is widely assumed that this complex is essential for asbestos-induced cancers. Here, we report that acute interleukin-1β production and recruitment of immune cells into peritoneal cavity were significantly decreased in the NLRP3-deficient mice after the administration of asbestos. However, NLRP3-deficient mice displayed a similar incidence of malignant mesothelioma and survival times as wild-type mice. Thus, early inflammatory reactions triggered by asbestos are NLRP3-dependent, but NLRP3 is not critical in the chronic development of asbestos-induced mesothelioma. Notably, in a two-stage carcinogenesis-induced papilloma model, NLRP3-deficient mice showed a resistance phenotype in two different strain backgrounds, suggesting a tumour-promoting role of NLRP3 in certain chemically-induced cancer types.
authors.affiliation: Cancer Immunology Program, Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne, Victoria, Australia.
authors.forename: Melvyn T
authors.initials: MT
authors.lastname: Chow
authors.forename: Jürg
authors.initials: J
authors.lastname: Tschopp
authors.forename: Andreas
authors.initials: A
authors.lastname: Möller
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Smyth
mesh_terms: D000818:Animals; D001194:Asbestos / Q000009:adverse effects; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002465:Cell Movement / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D004781:Environmental Exposure / Q000009:adverse effects; D005260:Female; D006801:Humans; D007249:Inflammation / Q000150:complications; D053583:Interleukin-1beta / Q000378:metabolism; D008654:Mesothelioma / Q000209:etiology / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D010212:Papilloma / Q000139:chemically induced / Q000276:immunology*; D010537:Peritoneum / Q000276:immunology / Q000473:pathology; D010997:Pleural Neoplasms / Q000209:etiology / Q000276:immunology*; D012878:Skin Neoplasms / Q000139:chemically induced / Q000276:immunology*
chemical_list: D002352:Carrier Proteins; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D001194:Asbestos