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Infection and Immunity, August 2008, p. 3651-3656, Vol. 76, No. 8
0019-9567/08/$08.00+0     doi:10.1128/IAI.00358-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Interleukin-12 (IL-12) and IL-23 Induction of Substance P Synthesis in Murine T Cells and Macrophages Is Subject to IL-10 and Transforming Growth Factor β Regulation{triangledown}

Arthur Blum, Tommy Setiawan, Long Hang, Korynn Stoyanoff, and Joel V. Weinstock*

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tufts New England Medical Center, Boston, Massachusetts 02111

Received 18 March 2008/ Returned for modification 19 April 2008/ Accepted 19 May 2008

Substance P is a tachykinin that enhances pathways of inflammation. Leukocytes at sites of intestinal inflammation make substance P. This study explored the role of interleukin-12 (IL-12), IL-23, and the regulatory cytokines IL-10 and transforming growth factor β (TGF-β) in controlling leukocyte substance P production. In murine schistosomiasis, it was found that IL-12 and IL-23 drive substance P gene expression and peptide synthesis in murine splenic T cells and macrophages, respectively. Cytokine induction of substance P synthesis both in T cells and in macrophages depends on intracellular NF-{kappa}B activation and is Stat4 independent. IL-10 inhibits T-cell substance P production, while TGF-β blocks macrophage substance P expression. Intestinal macrophages also produce substance P, subject mostly to IL-23 and TGF-β regulation. Hemokinin is another tachykinin with homology to substance P. Macrophages and T cells make hemokinin, but hemokinin production is not subject to IL-12 or IL-23 regulation.


* Corresponding author. Mailing address: Division of Gastroenterology (233), Tufts New England Medical Center, Boston, MA 02111. Phone: (617) 636-8387. Fax: (617) 636-4505. E-mail: jweinstock2{at}Tufts-NEMC.org

{triangledown} Published ahead of print on 27 May 2008.

Editor: S. R. Blanke


Infection and Immunity, August 2008, p. 3651-3656, Vol. 76, No. 8
0019-9567/08/$08.00+0     doi:10.1128/IAI.00358-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.