NLRP3 promotes inflammation-induced skin cancer but is dispensable for asbestos-induced mesothelioma

Immunol Cell Biol. 2012 Nov;90(10):983-6. doi: 10.1038/icb.2012.46. Epub 2012 Sep 25.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Asbestos / adverse effects
  • Carrier Proteins / genetics
  • Carrier Proteins / immunology
  • Carrier Proteins / metabolism*
  • Cell Movement / genetics
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / immunology
  • Disease Models, Animal
  • Environmental Exposure / adverse effects
  • Female
  • Humans
  • Inflammation / complications
  • Interleukin-1beta / metabolism
  • Mesothelioma / etiology
  • Mesothelioma / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Papilloma / chemically induced
  • Papilloma / immunology*
  • Peritoneum / immunology
  • Peritoneum / pathology
  • Pleural Neoplasms / etiology
  • Pleural Neoplasms / immunology*
  • Skin Neoplasms / chemically induced
  • Skin Neoplasms / immunology*

Substances

  • Carrier Proteins
  • Interleukin-1beta
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • Asbestos