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 beta regulation.
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 beta (TGF-beta) 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-kappaB activation and is Stat4 independent. IL-10 inhibits T-cell substance P production, while TGF-beta blocks macrophage substance P expression. Intestinal macrophages also produce substance P, subject mostly to IL-23 and TGF-beta 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.
Blum
Arthur
A
Division of Gastroenterology (233), Tufts New England Medical Center, Boston, MA 02111, USA.
Setiawan
Tommy
T
Hang
Long
L
Stoyanoff
Korynn
K
Weinstock
Joel V
JV
D000818:Animals; D020869:Gene Expression Profiling; D016753:Interleukin-10 / Q000378:metabolism*; D018664:Interleukin-12 / Q000276:immunology*; D053759:Interleukin-23 / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D050797:STAT4 Transcription Factor / Q000235:genetics / Q000378:metabolism; D012552:Schistosomiasis / Q000276:immunology; D013154:Spleen / Q000276:immunology; D013373:Substance P / Q000096:biosynthesis*; D013601:T-Lymphocytes / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D053759:Interleukin-23; D016328:NF-kappa B; D050797:STAT4 Transcription Factor; C494091:Stat4 protein, mouse; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D018664:Interleukin-12; D013373:Substance P