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

Our plain-English summary of NLRP3 promotes inflammation-induced skin cancer but is dispensable for asbestos-induced mesothelioma, by M.T. Chow, J. Tschopp, A. Möller, et al (Immunology and Cell Biology, 2012).

The study

• Authors: M.T. Chow, J. Tschopp, A. Möller, M.J. Smyth
• Journal: Immunology and Cell Biology
• Published: 2012;90(10):983-6
• Cited by: 66 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

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.

In plain English

This short communication reported a mouse experiment testing whether NLRP3 is needed for asbestos to cause malignant mesothelioma. NLRP3 is part of an immune sensor (the NLRP3 inflammasome) that responds to asbestos. The authors injected 3 mg of asbestos into the peritoneal (abdominal) cavity of normal (wild-type) mice and of mice lacking NLRP3. The article does not name the fiber type. About 21 to 22 mice per group were followed for up to 24 months. Median survival was 417 days in both groups, and survival did not differ statistically. Frank malignancy was found in 6 of 21 wild-type and 7 of 22 NLRP3-deficient mice. Three days after injection, NLRP3-deficient mice had fewer immune cells in the peritoneum and lower blood levels of the signalling molecule interleukin-1 beta. By day 9 the immune-cell differences were no longer detected. In a separate chemical skin-cancer model, NLRP3-deficient mice were more resistant to skin papillomas. The authors concluded that NLRP3 is required for the early inflammatory response to asbestos but is dispensable for asbestos-induced mesothelioma. They said they could not rule out low-level chronic inflammation that does not depend on NLRP3.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Animal experiment in mice (short communication); asbestos injected into the peritoneum of wild-type and NLRP3-deficient mice, plus a separate two-stage chemical skin carcinogenesis (DMBA/TPA) papilloma model
• Who was studied: Wild-type and NLRP3-deficient mice (C57BL/6 and BALB/c backgrounds), 6 to 8 weeks old at injection. The mesothelioma groups had 21 to 22 mice each and were followed for up to 24 months. The inflammation experiments used four to five mice per group. The skin papilloma experiment used 20 mice per group.
• Exposure: A single intraperitoneal injection of 3 mg asbestos in solution (fiber type not specified in the article). The skin model used topical DMBA followed by TPA twice weekly for 20 weeks.
• Main results:
  • Median survival after asbestos injection was 417 days for both wild-type and NLRP3-deficient mice. Long-term survival was not statistically different between the groups.
  • Frank malignancy (malignant mesothelioma) was found in 6 of 21 wild-type mice and 7 of 22 NLRP3-deficient mice. The authors described this incidence as similar.
  • On day 3 after asbestos injection, NLRP3-deficient mice had significantly fewer NK cells, CD4+ T cells, CD8+ T cells, macrophages and neutrophils in the peritoneum than wild-type mice.
  • By day 9 after asbestos injection, no detectable differences in peritoneal immune cell types were seen between the two strains. Cell infiltrates were also comparable at day 30.
  • Three days after exposure, only serum IL-1 beta was significantly lower in NLRP3-deficient mice. By day 9, serum IL-1 alpha, IL-1 beta and TNF-alpha were significantly reduced in NLRP3-deficient mice compared with wild-type mice.
  • In the DMBA/TPA skin papilloma model, NLRP3-deficient C57BL/6 mice were statistically more resistant to papilloma formation than wild-type mice. Similar results were obtained in the BALB/c background.
• The authors' conclusion: The authors concluded that NLRP3 is required for the early inflammatory response to asbestos but is dispensable for the development of asbestos-induced mesothelioma. They suggested that the early inflammatory response to asbestos is not critical to later cancer development. They also suggested that NLRP3 promotes certain chemically induced cancers, such as the skin papillomas in this model.
• Limitations the authors state:
  • The authors could not exclude NLRP3-independent chronic inflammation playing a part in asbestos-induced mesothelioma.
  • The authors stated that no experimental tools were available to monitor low-level chronic inflammation over the long tumour development period.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Inflammation, Mesothelioma, Asbestos Exposure, Peritoneal Cavity, Carcinogenesis.

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