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

Joel V. Weinstock, Arthur Blum, Ahmed Metwali, David Elliott, Nigel Bunnett, Razvan Arsenescu

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Abstract

Substance P (SP) is a proinflammatory molecule that interacts with a neurokinin 1 receptor (NK-1R), which is on T cells and helps control IFN-γ production. IL-10 -/- mice given a nonsteroidal anti-inflammatory drug (NSAID) develop Th1 colitis. We studied the importance of SP and NK-1R in this colitis model. LP T cells were isolated to study their NK-1R expression. LP T cells from IL-10 -/- mice expressed NK-1R and produced IFN-γ only after NSAID treatment and induction of colitis. LP T cells from NSAID-treated wild-type controls or from age-matched untreated IL-10 -/- animals did not express NK-1R or produce IFN-γ. Experiments showed that IL-12 induced NK-1R transcription in CD4 + T cells cultured in vitro. However, T cells cultured with IL-12 and IL-10 did not express NK-1R. IL-10 also down-modulated ongoing NK-1R expression. Mice given NK-1R antagonist after NSAID induction of severe colitis showed nearly complete reversal of inflammation, and LP T cells ceased IFN-γ secretion. Thus, intestinal inflammation in IL-10 -/- mice is associated with the appearance of NK-1R in mucosal T cells, and an interplay between IL-12 and IL-10 regulates T cell NK-1R transcription. NK-1R antagonist reverses ongoing intestinal inflammation attesting to the importance of SP and its receptor in mucosal inflammation.

Original languageEnglish (US)
Pages (from-to)3762-3767
Number of pages6
JournalJournal of Immunology
Volume171
Issue number7
DOIs
StatePublished - Oct 1 2003
Externally publishedYes

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Neurokinin-1 Receptors
Colitis
Substance P
Knockout Mice
Interleukin-10
T-Lymphocytes
Anti-Inflammatory Agents
Interleukin-12
Neurokinin-1 Receptor Antagonists
Inflammation
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Weinstock, J. V., Blum, A., Metwali, A., Elliott, D., Bunnett, N., & Arsenescu, R. (2003). Substance P regulates Th1-type colitis in IL-10 knockout mice. Journal of Immunology, 171(7), 3762-3767. https://doi.org/10.4049/jimmunol.171.7.3762
Weinstock, Joel V. ; Blum, Arthur ; Metwali, Ahmed ; Elliott, David ; Bunnett, Nigel ; Arsenescu, Razvan. / Substance P regulates Th1-type colitis in IL-10 knockout mice. In: Journal of Immunology. 2003 ; Vol. 171, No. 7. pp. 3762-3767.
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Weinstock, JV, Blum, A, Metwali, A, Elliott, D, Bunnett, N & Arsenescu, R 2003, 'Substance P regulates Th1-type colitis in IL-10 knockout mice', Journal of Immunology, vol. 171, no. 7, pp. 3762-3767. https://doi.org/10.4049/jimmunol.171.7.3762

Substance P regulates Th1-type colitis in IL-10 knockout mice. / Weinstock, Joel V.; Blum, Arthur; Metwali, Ahmed; Elliott, David; Bunnett, Nigel; Arsenescu, Razvan.

In: Journal of Immunology, Vol. 171, No. 7, 01.10.2003, p. 3762-3767.

Research output: Contribution to journalArticle

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AU - Blum, Arthur

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AU - Elliott, David

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