【摘 要】
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Ami To investigate PGE2 and TNFalpha signaling pathway involving in the maturation and activation of bone marrow dendritic cells (DCs) and the effect of CP25.Method Bone marrow DCs were isolated and s
【机 构】
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Institute of Clinical Pharmacology,Anhui Medical University,Key Laboratory of Anti-inflammatory and
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Ami To investigate PGE2 and TNFalpha signaling pathway involving in the maturation and activation of bone marrow dendritic cells (DCs) and the effect of CP25.Method Bone marrow DCs were isolated and stimulated by PGE2 and TNFalpha respectively.The markers of maturation and activation expressed on DCs, such as CD40, CD80, CD83, CD86, MHCⅡ, and the ability of antigen uptake of DCs were analyzed by flow cytometry.The proliferation of T cells cocultured with DCs, the signaling pathways of PGE2EP4cAMP and TNFalphaTRADDTRAF2NFκB in DCs were analyzed.Result Both PGE2 and TNFalpha upregulated the expressions of CD40, CD80, CD83, CD86, and MHCⅡ, decreased the antigen uptake of DCs, and DCs stimulated by PGE2 or TNFalpha could increase T cell proliferation.CP25 (105, 106, 107 mol/L) decreased significantly the expressions of CD40, CD80, CD83, CD86 and MHCⅡ, increased the antigen uptake of DCs, and suppressed T cell proliferation induced by DCs.PGE2 increased the expressions of EP4, NFκB and downregulated cAMP level of DCs.TNFalpha could also upregulate TNFR1, TRADD, TRAF2, and NFκB expression of DCs.CP25 (105,106, 107 mol/L) decreased the expressions of EP4 and NFκB, increased cAMP level in DCs stimulated by PGE2.CP25 (105, 106, 107 moL/L) also could downregulate significantly TNFR1, TRADD, TRAF2, and NFκB expression in DCs stimulated by TNFalpha.Conclusion PGE2 and TNFalpha could enhance DCs functions by mediating PGE2EP4cAMP pathway, TNFalphaTNFR1TRADDTRAF2NFκB pathway respectively.CP25 might inhibit the function of DCs through regulating PGE2EP4cAMP and TNFalphaTNFR1TRADDTRAF2NFκB pathways.
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