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The Cell-specific Role Of MKP-1 In Psoriasis Pathogenesis And Effects Of CK2 On The T Cell Differentiation

Posted on:2018-04-15Degree:MasterType:Thesis
Country:ChinaCandidate:W H ZhaoFull Text:PDF
GTID:2404330590968752Subject:Basic Medicine
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Objective: It has been reported that MKP-1 is involved in the development of psoriasis,but the cellular mechanism is largely unknown.In this study,we want to investigate the cell-specific role of MKP-1 in the pathogenesis of psoriasis.Methods: 1.IMQ was topically applied on the ears of WT and MKP-1 KO mice,and the changes of ear thickness was measured.At the peak of this disease,cell infiltration in the ears and draining lymphonodes was determined by FACS.The mRNA levels of related genes were deteted by Real-time PCR;2.Two different chimeras were generated to define the cell type using methods mentioned above;3.In vitro,BMDMs were cultured and stimulated with R848 to detect the mRNA expression and the protein production.Results: 1.MKP-1 KO mice were more susceptible to IMQ-induced psoriasiform skin inflammation with more cell infiltration in the ears,especially macrophages and increased expression of IL-1b;2.Deletion of MKP-1 in hematopoietic-and non-hematopoietc-drived cells showed more severity of the disease,such as increased ear thickness and more cell infiltration;3.In vitro,stimulated with R848,macrophages from MKP-1 KO mice showed more expression of IL-1b and the phosholation of p38 and JNK was upregulated.Treated with inhibitors of p38 and JNK,the upregulation of IL-1b was disappeared between the macrophages from WT and MKP-1 KO mice.Conclusion: MKP-1 from both hematopoitic-and non-hematopoitic-drived cells can suppress the development of psoriasis;MKP-1 in macrophages may downregulate the expression of IL-1b by suppressing the activity of p38 and JNK to alleviate the severity of psoriasis.Objective: In this study,we investigated the effects of CK2 on the T cell differentiation;Methods: We added TBB(inhibitor of CK2)into the T cell differentiation systems.5 days after,we harvested the cells to perform intracellular staining(IFN?,IL-4 and IL-17)and Foxp3 staning to detect the T cell differentiation;Results: CK2 promotes Th17 differentiation and suppresses Treg differentiaton in a dose-dependent manner,but has effects on the differentiation of Th1 and Th2;Conclusions: Theses results showed that CK2 has an important role in T cell differentiation;...
Keywords/Search Tags:Psoriasiform skin inflammation, MKP-1, macrophage, IL-1b, CK2, TBB, T cell differentiation
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