Substance P regulates somatostatin expression in inflammation

Arthur M Blum; David E Elliott; Ahmed Metwali; Jie Li; Khurram Qadir; Joel V Weinstock

doi:10.4049/jimmunol.161.11.6316

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Substance P regulates somatostatin expression in inflammation

Journal article

Peer reviewed

Substance P regulates somatostatin expression in inflammation

Arthur M Blum, David E Elliott, Ahmed Metwali, Jie Li, Khurram Qadir and Joel V Weinstock

The Journal of immunology (1950), Vol.161(11), pp.6316-6322

12/01/1998

DOI: 10.4049/jimmunol.161.11.6316

PMID: 9834121

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Abstract

Substance P (SP) and somatostatin (SOM) are made at mucosal surfaces and sites of inflammation. There is a SP/SOM immunoregulatory circuit that modulates the IFN-gamma response in murine schistosomiasis. SP enhances, while SOM decreases, IFN-gamma secretion. Various inflammatory mediators induce macrophages to make SOM, but no known factor limits this expression. It was discovered that SP regulates SOM synthesis. Splenocytes from normal, uninfected mice cultured with LPS, IFN-gamma, or IL-10 for 4 h strongly expressed SOM mRNA, but failed to do so in the presence of SP. The inhibition with 10(-9) M SP was > 85% shown by quantitative PCR. Also, splenocyte SOM content decreased from 1048 +/- 275 to < 10 pg/4 x 10(8) cells following SP exposure. Immunohistochemistry identified SOM solely within splenic macrophages following cytokine stimulation. Mice infected with Schistosoma mansoni form granulomas in the liver and intestines resulting from deposition of parasite eggs in these organs. The granulomas contain macrophages that make SOM constitutively. SP at 10(-8) M decreased SOM mRNA expression > 90% in dispersed granuloma cells cultured for 4 h or longer. Specific SP receptor antagonists blocked SP suppression of SOM expression in splenocytes and dispersed granuloma cells, showing that an authentic SP receptor mediated the regulation. Additional studies revealed that IL-4 antagonized the SP effect in the spleen. It is concluded that in granulomas and splenocytes from mice with schistosomiasis and in splenocytes from uninfected animals that 1) SP inhibits macrophage SOM induction and ongoing expression at the mRNA and protein levels acting through the SP receptor, and 2) IL-4 can antagonizes this SP effect.

T-Lymphocytes - physiology

Granuloma - metabolism

Schistosomiasis mansoni - immunology

Protein Precursors - antagonists & inhibitors

RNA, Messenger - biosynthesis

RNA, Messenger - antagonists & inhibitors

Mice, Inbred CBA

Female

Inflammation Mediators - antagonists & inhibitors

Inflammation Mediators - physiology

Interleukin-4 - physiology

Substance P - antagonists & inhibitors

Somatostatin - genetics

Protein Precursors - genetics

Mice, Inbred C57BL

B-Lymphocytes - physiology

Somatostatin - antagonists & inhibitors

Mice, Transgenic

Spleen - cytology

Receptors, Neurokinin-1 - physiology

Somatostatin - biosynthesis

Schistosomiasis mansoni - metabolism

Macrophages - metabolism

Animals

Spleen - metabolism

Protein Precursors - biosynthesis

Substance P - physiology

Granuloma - immunology

Mice

Details

Title: Subtitle: Substance P regulates somatostatin expression in inflammation
Creators: Arthur M Blum - Department of Internal Medicine, University of Iowa, Iowa City 52242, USA
David E Elliott
Ahmed Metwali
Jie Li
Khurram Qadir
Joel V Weinstock
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.161(11), pp.6316-6322
DOI: 10.4049/jimmunol.161.11.6316
PMID: 9834121
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Grant note: DK38327 / NIDDK NIH HHS DK25295 / NIDDK NIH HHS DK02428 / NIDDK NIH HHS
Language: English
Date published: 12/01/1998
Academic Unit: Gastroenterology and Hepatology; Internal Medicine
Record Identifier: 9984094759102771

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