Regulation of PGE2 signaling pathways and TNF-alpha signaling pathways on the function of bone marrow-derived dendritic cells and the effects of CP-25  

出　　处：《中国药理学通报》2015年第B11期26-27,共2页Chinese Pharmacological Bulletin

摘　　要：Ami To investigate PGE2 and TNF-alpha signaling pathway involving in the maturation and activation of bone marrow dendritic cells （DCs） and the effect of CP-25. Method Bone marrow DCs were isolated and stim- ulated by PGE2 and TNF-alpha respectively. The markers of maturation and activation expressed on DCs, such as CD40, CD80, CD83, CD86, MHC-II, and the ability of antigen uptake of DCs were analyzed by flow cytometry. The proliferation of T cells co-cultured with DCs, the signaling pathways of PGE2-EP4-cAMP and TNF-alpha- TRADD-TRAF2-NF-KB in DCs were analyzed. Result Both PGE2 and TNF-alpha up-regulated the expressions of CD40, CD80, CD83, CD86, and MHC-II, decreased the antigen uptake of DCs, and DCs stimulated by PGE2 or TNF-alpha could increase T cell proliferation. CP-25 （ 10 -5, 10 -6 , 10 -7 mol/L ） decreased significantly the ex- pressions of CD40, CD80, CD83, CD86 and MHC- ]I , increased the antigen uptake of DCs, and suppressed T cell proliferation induced by DCs. PGE2 increased the expressions of EP4, NF-KB and down-regulated cAMP level of DCs. TNF-alpha could also up-regulate TNFR1, TRADD, TRAF2, and NF-KB expression of DCs. CP-25 （10^-5, 10^-6, 10^-7 mol/L） decreased the expressions of EP4 and NF-KB, increased cAMP level in DCs stimulated by PGE2. CP-25 （10^-5 10^-6 10^-7 mol/L） also could down-regulate significantly TNFR1 TRADD TRAF2 and NF-KB expression in DCs stimulated by TNF-alpha. Conclusion PGE2 and TNF-alpha could enhance DCs func- tions by mediating PGE2-EP4-cAMP pathway, TNF-alpha-TNFR1-TRADD-TRAF2-NF-KB pathway respectively. CP-25 might inhibit the function of DCs through regulating PGE2-EP4-cAMP and TNF-alpha-TNFR1-TRADD- TRAF2-NF-KB pathways.

关 键 词：PGE2 TNF-ALPHA EP4 TRAF2 CP-25 DENDRITIC cells 

分 类 号：R[医药卫生]