4.3 Article

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

Journal

IMMUNOLOGY AND CELL BIOLOGY
Volume 90, Issue 10, Pages 983-986

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/icb.2012.46

Keywords

asbestos; mesothelioma; inflammasome; inflammation; skin; cytokine

Funding

  1. National Health and Medical Research Council (NH & MRC) of Australia Centre for Research Excellence in Asbestos Related Diseases
  2. NBCF Research Fellowship
  3. AICR
  4. Cancer Research Institute PhD Scholarship
  5. Swiss National Research Foundation, Institute for Arthritis Research, Apo-Sys consortium

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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-1 beta 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. Immunology and Cell Biology (2012) 90, 983-986; doi: 10.1038/icb.2012.46; published online 25 September 2012

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