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Substance P and the regulation of inflammation in infections and inflammatory bowel disease
Author(s) -
Weinstock J. V.
Publication year - 2015
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.12428
Subject(s) - tachykinin receptor 1 , immune system , proinflammatory cytokine , interleukin 10 , inflammation , immunology , receptor , interleukin 12 , internalization , biology , inflammatory bowel disease , substance p , medicine , disease , cytotoxic t cell , neuropeptide , in vitro , biochemistry
Substance P (SP) and its natural analogue hemokinin‐1 (HK1) are produced by lymphocytes and macrophages, and at times B cells. These peptides are an important component of the immune response during several infections and in inflammatory bowel disease (IBD). The synthesis of SP and HK1 in leucocytes is subject to immune regulation. IL 12 and IL 23 stimulate T cells and macrophages to make SP respectively. The cytokines driving HK1 production are not presently defined. These peptides act through a shared receptor called neurokinin‐1. T cells, macrophages and probably other immune cell types can express this receptor. Several cytokines IL 12, IL 18 and TNF α as well as T‐cell antigen receptor activation induce neurokinin‐1 receptor expression on T cells, while IL 10 blocks receptor display. TGF β delays internalization of the SP/neurokine‐1R complex on T cells resulting in stronger receptor signalling. One of the functions of SP and neurokinin‐1 receptor is to enhance T cell IFN γ and IL 17 production, amplifying the proinflammatory response. Thus, SP and HK1 have overlapping functions and are part of a sophisticated immune regulatory circuit aimed at amplifying inflammation at mucosal surfaces and in other regions of the body as shown in animal models of infection and IBD.