IL-12 induction of mRNA encoding substance P in murine macrophages from the spleen and sites of inflammation

Razvan Arsenescu; Arthur M Blum; Ahmed Metwali; David E Elliott; Joel V Weinstock

doi:10.4049/jimmunol.174.7.3906

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IL-12 induction of mRNA encoding substance P in murine macrophages from the spleen and sites of inflammation

Journal article

Open access

Peer reviewed

IL-12 induction of mRNA encoding substance P in murine macrophages from the spleen and sites of inflammation

Razvan Arsenescu, Arthur M Blum, Ahmed Metwali, David E Elliott and Joel V Weinstock

The Journal of immunology (1950), Vol.174(7), pp.3906-3911

04/01/2005

DOI: 10.4049/jimmunol.174.7.3906

PMID: 15778345

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Abstract

Substance P (SP), a neuropeptide, interacts with the neurokinin 1 receptor (NK-1R) on immune cells to help control IFN-gamma production. In murine schistosomiasis mansoni, schistosome worms produce ova that incite focal Th2-type granulomatous inflammation within the liver and intestines. Normal gut is characterized by a controlled state of inflammation. IL-10 knockout mice develop chronic Th1-type colitis spontaneously. Both schistosome granulomas and gut mucosa display an SP immune regulatory circuit. However, the origin and regulation of SP production at these sites of inflammation are poorly understood. Macrophages are a potential source of SP. We therefore studied macrophages (F4/80(+)) from these models of inflammation. SP mRNA (preprotachykinin A (PPT A)) was detected within the schistosome granuloma, spleen, and lamina propria macrophages. Compared with those from wild-type mice, granuloma macrophages from STAT6(-/-) mice had 10-fold higher PPT A mRNA expression, whereas in STAT4(-/-) animals, PPT A mRNA expression was nearly abolished. IL-12 signals via STAT4 to induce Th1-type inflammation. It was demonstrated that IL-12, but not IL-18, induces SP mRNA expression in resting splenic macrophages from Schistosoma-infected mice and in wild-type lamina propria mononuclear cells. Thus, macrophages are a source for SP at these sites of chronic inflammation, and IL-12 and STAT4 are regulators of macrophage SP mRNA expression.

Inflammation - pathology

Macrophages - chemistry

DNA-Binding Proteins - physiology

Spleen - immunology

Gene Expression Regulation

Interleukin-12 - physiology

RNA, Messenger - analysis

Inflammation - immunology

Mice, Inbred Strains

Mice, Knockout

Trans-Activators - physiology

Animals

STAT4 Transcription Factor

Substance P - genetics

Granuloma - immunology

Mice

Schistosomiasis - immunology

Macrophages - immunology

Details

Title: Subtitle: IL-12 induction of mRNA encoding substance P in murine macrophages from the spleen and sites of inflammation
Creators: Razvan Arsenescu - Department of Internal Medicine, University of Kentucky, Lexington, KY 40515, USA. razvan-arsenescu@uky.edu
Arthur M Blum
Ahmed Metwali
David E Elliott
Joel V Weinstock
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.174(7), pp.3906-3911
DOI: 10.4049/jimmunol.174.7.3906
PMID: 15778345
ISSN: 0022-1767
eISSN: 1550-6606
Grant note: DK38327 / NIDDK NIH HHS DK25295 / NIDDK NIH HHS DK02428 / NIDDK NIH HHS
Language: English
Date published: 04/01/2005
Academic Unit: Gastroenterology and Hepatology; Internal Medicine
Record Identifier: 9984094594302771

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