Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

T cell response to alloantigen is dependent not only on T cell receptor activation, but also upon co-stimulation through the CD28 receptor, as T cell receptor activation alone is insufficient for an optimal immune response. The CD28 receptor on helper T cells interacts with its ligand B7 on activated B cells/macrophages as the co-stimulus to support T cell activity. The natural ligand for CD28, B7 is expressed in both constituitive and inducible forms. Expression of the inducible form, B7.1 is the most co-stimulatory and may peak at 48 hr following antigen presentation. CTLA4Ig (a soluble CD28 receptor analog) binds both B7's and inhibits CD28 activation. This experiment was undertaken to examine the optimal time course of CTLA4Ig effect at or following antigen presentation. In vivo studies used a rat MHC mismatch heterotopic cardiac allograft transplant model (Brown-Norway to Lewis). Controls received no immunotherapy. Experimental recipients received CTLA4Ig (0.05 mg i.p.) the day of transplant only or had CTLA4Ig x 7-21 days begun at Day 0, 3, or 5 following transplant. Rejection was defined as a lack of allograft contraction. Allograft survival was best when CTLA4Ig was present on Day 2. These findings demonstrate that CTLA4Ig was most effective 48 hr following antigen presentation, perhaps reflecting induction of tolerance at a time of maximal CTLA4Ig/B7.1 blockade. CTLA4Ig given later, at a time when the recognition/rejection process has already begun was not as effective indicating the lack of immunosuppressive function of CTLA4Ig itself and confirms CTLA4Ig's mechanism of co-stimulation blockade.
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PMID:The time course of CTLAIg effect on cardiac allograft rejection. 866 Dec 18

The human colonic epithelial cell line HT-29 can be induced by a combination of the cytokines interleukin (IL)-1alpha, tumor necrosis factor alpha, and interferon-gamma to express the inducible form of nitric-oxide synthase (iNOS; Kolios, G., Brown, Z., Robson, R., Robertson, D. A. F., & Westwick, J. (1995) Br. J. Pharmacol. 116, 2866-2872). IL-13 is a potent inhibitor of cytokine-induced iNOS mRNA expression and nitric oxide generation in HT-29 cells via an unknown mechanism. We report here that in HT-29 cells, IL-13 induces a concentration and time-dependent increase in the formation of the lipid products of phosphatidylinositol (PtdIns) 3-kinase, namely phosphatidylinositol (3,4)-bisphosphate and phosphatidylinositol (3,4,5)-trisphosphate. IL-13 also induces a parallel concentration and time-dependent increase in the in vitro lipid kinase activity present in immunoprecipitates of the p85 regulatory subunit of PtdIns 3-kinase. In addition, we also demonstrate that IL-13 stimulates the tyrosine phosphorylation of the adaptor molecule insulin receptor substrate 1, which may facilitate receptor coupling to PtdIns 3-kinase. Both the increases in D-3 phosphatidylinositol lipids and the increased in vitro lipid kinase activity of p85 immunoprecipitates were inhibited by wortmannin and LY294002. Inhibition of the PtdIns 3-kinase activity was paralleled by a reversal of the ability of IL-13 to inhibit iNOS mRNA expression and nitrite generation in HT-29 cells. These data demonstrate that the activation of PtdIns 3-kinase by IL-13 is a key signal that is responsible for the inhibition of iNOS transcription in activated epithelial cells.
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PMID:Activation of phosphatidylinositol 3-kinase by interleukin-13. An inhibitory signal for inducible nitric-oxide synthase expression in epithelial cell line HT-29. 913 18

Normal aging is associated with chronic oxidative stress. In the basal ganglia, oxidative stress may contribute to the increased risk of Parkinson's disease in the elderly. Neurons are thought to actively utilize compensatory defense mechanisms, such as heat shock proteins (HSPs), to protect from persisting stress. Despite their protective role, little is known about HSP expression in the aging basal ganglia. The purpose of this study was to examine HSP expression in striatum, substantia nigra, globus pallidus and cortex in 6-, 18- and 30-month-old Fischer 344/Brown Norway rats. We found robust age-related increases in phosphorylated and total HSP25 in each brain region studied. Conversely, HSP72 (the inducible form of HSP70) was reduced with age, but only in the striatum. p38 MAPK, a protein implicated in activating HSP25, did not change with age, nor did HSC70 (the constitutive form of HSP70), or HSP60. These results suggest that HSP25 is especially responsive to age-related stress in the basal ganglia.
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PMID:Age-related changes in HSP25 expression in basal ganglia and cortex of F344/BN rats. 2014 90