Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A duodenal biopsy culture technique was used to investigate the effect of substance P on lymphokine secretion by the human gut associated lymphoid tissue. Duodenal biopsies of 7 healthy volunteers were cultured in 1 ml medium each with Pokeweed mitogen (1 microgram/ml) for 4 days at 37 degrees C. Substance P (SP) was added in concentrations ranging from 10(-12) M to 10(-6) M. Media were changed every day. Interleukin (IL)-1 beta, IL-2 and IL-2-receptor activities were determined by means of specific ELISAs. Values were referred to 5 mg biopsy weight and expressed as per cent change of basal Pokeweed mitogen-pulsed supernatant activities. 10(-8) M and 10(-6) M SP led to a decrease of IL-1 beta activity (78 +/- 13.9% and 62.8 +/- 17.1%, respectively, alpha = 0.01 each). In contrast, 10(-8) and 10(-10) M SP showed an increase in IL-2 activity up to 182.9 +/- 94.5% and 295.6 +/- 144.7%, respectively. 10(-6) M and 10(-8) M SP enhanced IL-2 receptor activities by 81.5 +/- 70% and 40.9 +/- 11.8%, respectively (alpha = 0.05). The present data demonstrate for the first time distinct SP-mediated effects on lymphokine activities in supernatants of cultured human duodenal biopsies.
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PMID:Substance P modulates lymphokine activities in supernatants of cultured human duodenal biopsies. 246 74

Substance P (SP) plays a major role in the regulation of the interaction between immune and nervous systems. SP administration stimulates Con A-induced proliferation of spleen and peripheral blood lymphocytes from normal and neonatally capsaicin treated rats, which correlated with enhanced IL-2 production and expression of activation antigens such as IL-2 receptor alpha chain (CD25) and RT1B MHC class II molecule. Moreover, SP markedly increased the percentage of CD5+ and CD4+ T lymphocytes in the peripheral blood of capsaicin-treated rats. Concomitant administration of SP with the non-peptide Neurokinin-1 receptor (NK1R) antagonist SR140333 completely inhibited the SP-mediated augmentation of Con A-induced PBL proliferation and IL-2 production as well as of CD4+ CD25+ and CD4+ RT1B+ T cell numbers in normal and capsaicin-treated rats. SR 140333 also blocked the increased percentage of peripheral blood CD4+ T cells induced by SP in capsaicin-treated rats.
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PMID:Neurokinin type-1 receptor antagonist inhibits enhancement of T cell functions by substance P in normal and neuromanipulated capsaicin-treated rats. 1037 65

The activity of substance P (SP) in the rat thymus seems to be tightly controlled by its bioavailability. In this study, we provide evidence for the expression of the SP-degrading enzyme, neutral endopeptidase (NEP)/CD10, by rat thymocyte subsets, and we illustrate its involvement in the in vivo SP/neurokinin-1 receptor (NK(1)R)-mediated regulation of thymocyte survival and proliferation. NEP/CD10 was expressed at both mRNA and protein levels on a substantial portion (45.5%) of CD5(+) thymocytes, namely on the CD4(+)CD8(+) (double positive; DP) and CD4(+) subsets. Continuous administration of thiorphan, a specific NEP/CD10 inhibitor, by means of miniosmotic pumps, enhanced rat thymocyte preprotachykinin-A (PPT-A) and NK(1)R mRNA expression as well as SP and NK(1)R protein levels in an NK(1)R-dependent manner. Thiorphan increased CD10(+)CD4(+) and CD10(+)DP thymocyte numbers, and an NK(1)R antagonist, (S)1-{2-[3(3-4-dichlorophenyl)-1-(3-iso-propoxyphenylacetyl)-piperidine-3-yl]ethyl}-4-pheny-1-azoniabicyclo[2.2.2]octane, chloride (SR140333), abrogated these stimulatory effects. In addition, the NEP/CD10 inhibitor stimulated interleukin (IL)-2 production, IL-2 receptor alpha chain expression, and concanavalin A-induced proliferation of CD5(+) thymocytes, and it inhibited spontaneous and NK(1)R-dependent thymocyte apoptosis. The thiorphan-protective antiapoptotic and proliferative effects involved the activation of Akt serine-threonine kinase, subsequent up-regulation of survivin mRNA, down-regulation of procaspase-3 mRNA levels, and suppression of caspase-3 activity, which were inhibited by SR140333 and mimicked by exogenous SP administration. Overall, our findings suggest that by controlling SP availability, NEP/CD10 negatively regulates thymocyte homeostasis and development.
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PMID:Thiorphan-induced survival and proliferation of rat thymocytes by activation of Akt/survivin pathway and inhibition of caspase-3 activity. 1862 88