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

• Published in: Infection and Immunity Vol. 76; no. 8; pp. 3651 - 3656
• Main Authors: Blum, Arthur, Setiawan, Tommy, Hang, Long, Stoyanoff, Korynn, Weinstock, Joel V
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for Microbiology 01.08.2008; American Society for Microbiology (ASM)
• Subjects: Animals; Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Gene Expression Profiling; Host Response and Inflammation; Interleukin-10 - metabolism; Interleukin-12 - immunology; Interleukin-23 - immunology; Macrophages - immunology; Mice; Microbiology; NF-kappa B - genetics; NF-kappa B - metabolism; Schistosoma; Schistosomiasis - immunology; Spleen - immunology; STAT4 Transcription Factor - genetics; STAT4 Transcription Factor - metabolism; Substance P - biosynthesis; T-Lymphocytes - immunology; Transforming Growth Factor beta - metabolism; Microbiology; Transforming growth factor β; Substance P; Cytokine; Rodentia; Interleukin 12; Neuropeptide; Immunity; Vertebrata; Mammalia; Mouse; Interleukin 10; T-Lymphocyte; Tachykinin; Macrophage
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.00358-08

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-κB 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.