Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Substance P (SP) is a proinflammatory mediator implicated in inflammatory bowel disease (IBD) and other inflammatory states. SP acts by stimulating the neurokinin-1 receptor (NK-1R) on T lymphocytes and other cell types, and regulates these cells in a complex interplay with multiple cytokines. The mechanisms of interaction among these inflammatory mediators are not yet fully understood. Here, we demonstrate that function of the NK-1R, a member of the G protein-coupled receptor (GPCR) superfamily, is modulated by TGF-beta. The latter acts not on a GPCR but via serine-threonine kinase-class receptors. By flow confocal image analysis, we demonstrate that TGF-beta delays SP-induced NK-1R internalization on mucosal T cells isolated from a mouse model of IBD and on granuloma T cells in murine schistosomiasis. Furthermore, luciferase reporter-gene assays revealed that NK-1R stimulation activates the nuclear factor of activated T cell- and activator protein-1-dependent signaling pathways, which are known triggers of effector T-cell cytokine production. TGF-beta markedly increases SP-induced activation of these signaling cascades, suggesting that delayed NK-1R internalization results in enhanced signaling. Providing a link to amplified immune function, SP and TGF-beta, when applied in combination, trigger a strong release of the proinflammatory cytokines IFN-gamma and IL17 from intestinal inflammatory T cells, whereas either agonist alone shows no effect. These observations establish precedent that members of two distinct receptor superfamilies can interact via a previously unrecognized mechanism, and reveal a paradigm of GPCR transregulation that is relevant to IBD and possibly other disease processes.
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PMID:TGF-beta regulates T-cell neurokinin-1 receptor internalization and function. 2016 79

Chagas' disease is one of the most serious parasitic diseases of Latin America, with a social and economic impact far outweighing the combined effects of other parasitic diseases such as malaria, leishmaniasis and schistosomiasis. In the chronic phase of this disease, the destruction of enteric nervous system (ENS) components leads to megacolon development. Previous data presented that the regeneration tax in the ENS neurons is augmented in chagasic patients. Although, there are several neuronal types with different functions in the intestine a detailed study about the regeneration of every neuronal type was never performed before. Therefore, the aim of this study was to evaluate the regeneration tax of every neuronal cell type in the ENS from chagasic patients with megacolon and non-infected individuals. A neuronal regeneration marker (GAP-43) was used in combination with a pan-neuronal marker (Peripherin) and several neuropeptides markers (cChat, Substance P, NPY, VIP and NOS), and it was considered as positive just with the combination of these markers. Our results demonstrated that the regeneration levels of cChat, Substance P, and NPY were similar in chagasic patients and non-infected individuals. However, levels of VIP and NOS neuropeptides were increased in chagasic patients when compared with non-infected individuals. We believe that the augment in the regeneration occur due to an increased destruction of selective neuronal types. These results corroborates with previous studies that pointed out to selective destruction of VIP and NOS neurons in chagasic patients.
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PMID:Regenerative process evaluation of neuronal subclasses in chagasic patients with megacolon. 2322 Apr 99


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