Substance P regulates Th1-type colitis in IL-10 knockout mice

¹Division of Gastroenterology-Hepatology, Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA. joel-weinstock@uiowa.edu

|September 23, 2003

Summary

Substance P (SP) and its receptor (NK-1R) drive T-cell mediated colitis in IL-10(-/-) mice. Blocking NK-1R reversed inflammation, highlighting SP

Area of Science:

Background:

Substance P (SP) is a proinflammatory neuropeptide that binds to the neurokinin 1 receptor (NK-1R).
NK-1R is expressed on T cells and influences interferon-gamma (IFN-gamma) production.
Interleukin-10 (IL-10) deficient mice treated with NSAIDs develop Th1 colitis.

Purpose of the Study:

To investigate the role of SP and NK-1R in NSAID-induced Th1 colitis in IL-10(-/-) mice.
To elucidate the regulatory mechanisms of NK-1R expression on T cells in the context of intestinal inflammation.

Main Methods:

Isolation of lamina propria (LP) T cells from IL-10(-/-) and wild-type mice.
Assessment of NK-1R expression and IFN-gamma production by LP T cells.
In vitro culture of CD4+ T cells with IL-12 and IL-10 to study NK-1R transcription.
Administration of an NK-1R antagonist to NSAID-treated IL-10(-/-) mice.

Main Results:

LP T cells from NSAID-treated IL-10(-/-) mice expressed NK-1R and produced IFN-gamma, unlike controls.
IL-12 induced NK-1R transcription in CD4+ T cells, while IL-10 suppressed it.
Treatment with an NK-1R antagonist significantly reversed established colitis and IFN-gamma secretion.

Conclusions:

Intestinal inflammation in IL-10(-/-) mice is linked to NK-1R expression on mucosal T cells.
The interplay between IL-12 and IL-10 critically regulates T cell NK-1R transcription.
Targeting the SP/NK-1R pathway offers a potential therapeutic strategy for mucosal inflammation.

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