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The Effect Of Interleukin-4 On The Expression Of PI3K In Asthmatic Rat T Lymphocytes

Posted on:2008-04-12Degree:MasterType:Thesis
Country:ChinaCandidate:J Y CuiFull Text:PDF
GTID:2144360272469091Subject:Respiratory medicine
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ObjectiveAllergic asthma is characterized by a variable degree of airflow obstruction, airway hyperresponsness, mucus overproduction, and chronic airway inflammation. Many kinds of inflamed cell such as lymphocyte , Eos, neutrophil, mast and some kinds of celelular are component of the asthma airway inflammation. Thus persistent chronic inflammation and hyperresponsiveness of the airway are the fundamental characteristics of asthma. T cell is thought playing a crucial role in these processes and accordingly be undertaken in recent studies of the mechanism of asthma as a warm spot.Many signal transduction pathways participated in the processes of T lymphocyte cytological effect such as differentiation, activation, proliferation, survival and anti- apoptosis. These signal transduction pathways include Ras/MAPK pathways, PLC-γpathways, PI-3K/Akt pathways, PKC/NF-κB pathways, Jak/STAT pathways, etc. And there are some crosstalks between these signal transduction pathways which enable them co-influence a series cytological effect of T cell. And different pathway lay particular emphasis on different T subtype cell.Phosphatidylinositol 3-kinase (PI3K) is a key regulator of a variety of cellular functions from cytoskeletal organization, vesicular trafficking, and cell proliferation to apoptosis. And PI-3K/Akt signal transduction pathway one of the most important signal transduction pathway in T cell and thus has close relationships with the differentiation, the expression of activation, proliferation, survival and anti- apoptosis of T cell. It is the specific functions that it can promote the activation of T cell as a co-stimulate of CD28, regulate the expression of cyclin and cell multiplicaiton factor to maintain the regular cell cycle of T cell, rivalry P53 and Fas-induced apoptosis of T cell by regulating kinase activation associated signal transducter and the expression of apoptosis regulating factor, etc. Recent studies have showed that PI-3K/Akt signal transduction pathway has an important effect on the activation, cytokines synthesis and secretion , survival and anti- apoptosis of T subtype cell.IL-4 released by Th2 cells is believed play an important role in the process of proliferation and survival and differentiation of T cells. Phosphatidylinositol 3-kinase (PI-3K) transduce activation signals into cytoplasm through phosphorylating substrate. Some investigations have showed that PI3K/Akt signal transduction pathway participate in IL-4-mediated proliferation and differentiation of T cells and B cells and marrow progenitor cell. Thus, our study now is to explore the expression of PI-3K in T lymphocyte of asthmatic rat and the relationship between PI3K and IL-4.MethodsIn our experiment, we established rat asthmatic model, cultured T helper 2 cell in vitro and measured the expression of PI-3K and IL-4 in T cells and supernatants respectively by Western blotting. 40Wistar rats were randomly divided into 2 groups as normal control, asthmatic group T lymphocyte were isolated and purified from blood of each rat and were re-cultured and then re–divided into relevent groups. The expression of PI3K were measured by Western blotting.ResultsThere was no significant difference of the expression of PI3K in T lymphocytes was found between normal control group and IL-4 treated normal group and between asthmatic group and IL-4 plus inhibitor treated asthmatic group(p>0.05) , meanwhile there was significant difference between normal control group and asthmatic group(p<0.05). Significant difference was also found among asthmatic group, IL-4 treated asthmatic group and IL-4 plus inhibitor treated asthmatic group (p<0.05).ConclusionThe expression of PI3K in asthmatic rat T lymphocytes was increased by treatment of IL-4, hinting that IL-4 maybe play a partial role in the PI-3K signal transduction pathway in asthmatic T lymphocytes.
Keywords/Search Tags:phosphatidylinositol, 3-kinase, Asthma T lymphocyte, interleukin-4
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