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 journalArticle

184 Citations (Scopus)

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

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Inflammasomes
Interleukin-18
Colorectal Neoplasms
Inflammation
Carcinogenesis
Effector Caspases
Azoxymethane
Caspase 1
Dextran Sulfate
Tumor Burden
Causality
Colonic Neoplasms
Neoplasms
Colon
Proteins

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

IL-18 production downstream of the Nlrp3 inflammasome confers protection against colorectal tumor formation. / Zaki, Mohammad Hasan; Vogel, Peter; Body-Malapel, Mathilde; Lamkanfi, Mohamed; Kanneganti, Thirumala Devi.

In: Journal of Immunology, Vol. 185, No. 8, 15.10.2010, p. 4912-4920.

Research output: Contribution to journalArticle

Zaki, Mohammad Hasan ; Vogel, Peter ; Body-Malapel, Mathilde ; Lamkanfi, Mohamed ; Kanneganti, Thirumala Devi. / IL-18 production downstream of the Nlrp3 inflammasome confers protection against colorectal tumor formation. In: Journal of Immunology. 2010 ; Vol. 185, No. 8. pp. 4912-4920.
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