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Am J Physiol Gastrointest Liver Physiol. 2013 Feb 15;304(4):G381-9. doi: 10.1152/ajpgi.00357.2012. Epub 2012 Dec 20.

IL-33-induced alterations in murine intestinal function and cytokine responses are MyD88, STAT6, and IL-13 dependent.

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1
Department of Medicine and the Mucosal Biology Research Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

Erratum in

  • Am J Physiol Gastrointest Liver Physiol. 2013 Jun 15;304(12):G1137. Blanco, Joan Antoni Fernandez [corrected to Fernández-Blanco, Joan Antoni].

Abstract

IL-33 is a recently identified cytokine member of the IL-1 family. The biological activities of IL-33 are associated with promotion of Th2 and inhibition of Th1/Th17 immune responses. Exogenous IL-33 induces a typical "type 2" immune response in the gastrointestinal tract, yet the underlying mechanisms remain to be fully elucidated. In addition, the role of IL-33 in the regulation of gastrointestinal function is not known. The present study investigated IL-33-dependent intestinal immunity and function in mice. Exogenous IL-33 induced a polarized type 2 cytokine response in the intestine that was entirely MyD88 dependent but STAT6 and IL-13 independent. Mice injected with recombinant IL-33 exhibited intestinal smooth muscle hypercontractility, decreased epithelial responses to acetylcholine and glucose, and increased mucosal permeability. IL-33 effects on intestinal epithelial function were STAT6 dependent, and both IL-4 and IL-13 appeared to play a role. The effects on smooth muscle function, however, were attributable to both STAT6-dependent and -independent mechanisms. In addition, IL-13 induction of insulin-like growth factor-1 was implicated in IL-33-induced smooth muscle hypertrophy. Finally, alternative activation of macrophages induced by IL-33 revealed a novel pathway that is IL-4, IL-13, and STAT6 independent. Thus manipulating IL-33 or related signaling pathways represents a potential therapeutic strategy for treating inflammatory diseases associated with dysregulated intestinal function.

PMID:
23257921
PMCID:
PMC3566613
DOI:
10.1152/ajpgi.00357.2012
[Indexed for MEDLINE]
Free PMC Article
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