IAI Accepts, published online ahead of print on 27 May 2008

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Infect. Immun. doi:10.1128/IAI.00358-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

IL12 and IL23 Induction of Substance P Synthesis in Murine T cells and Macrophages is Subject to IL10 and TGF Regulation

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, MA

^* To whom correspondence should be addressed. Email: jweinstock2{at}Tufts-NEMC.org.

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 IL12, IL23 and the regulatory cytokines IL10 and TGFb in controlling leukocyte substance P production. In murine schistosomiasis, it was found that IL12 and IL23 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 macrophages depends on intracellular NFkB activation and is Stat4 independent. IL10 inhibits T cell substance P production, while TGFb blocks macrophage substance P expression. Intestinal macrophages also make substance P, subject mostly to IL23 and TGFb regulation. Hemokinin is another tachykinin with homology to substance P. Macrophages and T cells make hemokinin, but hemokinin production is not subject to IL12 or IL23 regulation.