IL-18 production downstream of the Nlrp3 inflammasome confers protection against colorectal tumor formation

Mohammad Hasan Zaki, Peter Vogel, Mathilde Body-Malapel, Mohamed Lamkanfi, Thirumala Devi Kanneganti

Research output: Contribution to journalArticlepeer-review

201 Scopus citations

Abstract

Colorectal cancer is a leading cause of cancer-related deaths worldwide. Chronic inflammation is recognized as a predisposing factor for the development of colon cancer, but the molecular mechanisms linking inflammation and tumorigenesis have remained elusive. Recent studies revealed a crucial role for the NOD-like receptor protein Nlrp3 in regulating inflammation through the assembly of proinflammatory protein complexes termed inflammasomes. However, its role in colorectal tumor formation remains unclear. In this study, we showed that mice deficient for Nlrp3 or the inflammasome effector caspase-1 were highly susceptible to azoxymethane/dextran sodium sulfate-induced inflammation and suffered from dramatically increased tumor burdens in the colon. This was a consequence of markedly reduced IL-18 levels in mice lacking components of the Nlrp3 inflammasome, which led to impaired production and activation of the tumor suppressors IFN-γ and STAT1, respectively. Thus, IL-18 production downstream of the Nlrp3 inflammasome is critically involved in protection against colorectal tumorigenesis.

Original languageEnglish (US)
Pages (from-to)4912-4920
Number of pages9
JournalJournal of Immunology
Volume185
Issue number8
DOIs
StatePublished - Oct 15 2010

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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