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The Change Of T-bet/GATA-3 Ratio In Chronic Sustained Model Of Experimental Autoimmune Encephalomyelitis And The Regulation Of Exogenous TGF-β1

Posted on:2008-03-18Degree:MasterType:Thesis
Country:ChinaCandidate:M WuFull Text:PDF
GTID:2144360215986164Subject:Neurology
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Objective: To investigate T-bet,GATA-3 mRNA dynamicexpression and T-bet/GATA-3 ratio in brains and spleens of inducedchronic non-remitting model of experimental autoimmune encepha-lomyelitis (EAE), and discuss the the role of T-bet,GATA-3 andT-bet/GATA-3 ratio in the pathogenesis of EAE/MS.Methods: 72 adult female C57BL/6 mice were randomly dividedinto the adjuvant-control group, EAE group, TGF-β1 treatment groupand treatment-control group. Each group mice should undergo threestages: catadrome phase,peak phase and chronic phase. MOG35-55 andCFA were injected into subcutaneous in EAE group. At the same time,besides treated MOG35-55 and CFA, TGF-β1 treatment group weresubcutaneously injected TGF-β1. In addition to immunization, PBS wasinjected subcutaneously in the treatment-control groups.At catadromephase, peak phase and chronic phase post-immunization, the ill mice weresacrificed. Whose T-bet mRNA and GATA-3 mRNA expression in brainsand spleens were detected using RT-PCR, and T-bet/GATA-3 ratio wascalculated by SPSS.Results: EAE group mice had developed a progressive paralysis,mice in TGF-β1 treatment group developed the ealier progressiveparalysis, which peaked at 17-22 days, and were more prone to recovery.The expression of T-bet mRNA of brains and spleens in EAE groupincreased from catadrome phase to peak phase, following by a descent inthe chronic phase. Contrast to the adjuvant-control group, the expressionof T-bet mRNA of brains and spleens singificant increased in each phaseduring the whole course. In TGF-β1 treatment group, the expression ofT-bet mRNA in each phase statistically decreased in contrast to EAEgroup and treatment-control group, while statistically increased contrast to the adjuvant-controIn in each phase.Contrast to the adjuvant-control group, the expression of GATA-3mRNA of brain and spleen in EAE group singificantly decreased duringthe whole course, while in TGF-β1 group, the expression of GATA-3decreased statistical in the TGF-β1 treatment group in contrast to EAEgroup and treatment-control group.T-bet/GATA-3 ratio in EAE group was higer than that ofadjuvant-control group in each phase. It increased from catadrome phaseto peak phase, following by a descent in the chronic phase. T-bet/GATA-3ratio in EAE group changed dramatically contrast to T-bet or GATA-3alone.In TGF-β1 treatment group, T-bet/GATA-3 ratio also changeddramatically contrast to T-bet or GATA-3 alone. The ratio of TGF-β1treatment group had complicated change, The ratio was higher than theratio in EAE group before high phase, then the ratio desreased faster thanthat of EAE group. In chronic phase, the ratio was lower than that ofEAE group.Conclusion:1. T-bet/GATA-3 ratio reflects the severity of disease of EAE moresensitively than T-bet or GATA-3 alone. Disequilibrium of theT-bet/GATA-3 ratio may be one of the important reason of MS.2. TGF-β1 directly or indirectly inhibits T-bet or GATA-3.Exogenous TGF-β1 probably plays a diphasic role in the different phaseof EAE. TGF-β1 induces to the ealier onset and is more prone torecovery.
Keywords/Search Tags:experimental autoimmune encephalomyelitis, multiple sclerosis, T-bet, GATA-3, transforming growth factor-β1
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