G protein coupled receptors signaling pathways implicate in inflammatory and immune response of rheumatoid arthritis / 中国药理学与毒理学杂志

G protein coupled receptors (GPCRs) are transmembrane receptor proteins, which allow signals to transfer across membrane. GPCRs include a large number of receptors, different receptors mediated different signaling pathways of GPCRs- adenylyl cyclase (AC)- cyclic adenosine 3' ,5'-monophosphate (cAMP), including β2 adrenergic receptors (β2- ARs)- AC- cAMP signaling pathways, E-prostanoid2/4 (EP2/4)-AC-cAMP signaling pathways. Regulatory proteins, such as G protein coupled receptor kinases (GRKs) and β-arrestins, play important modulatory roles in GPCRs signaling pathway. GPCRs signaling pathway and regulatory proteins implicate the pathogenesis process of inflammatory and immune response. Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovitis and accompanied with inflammatory and abnormal immune response. This article review the advances on GPCRs signaling pathway implicating in the inflammatory and immune response of RA.

CP-25 inhibits the functions of activated human B cells through regulating BAFF-TRAF2-NF-κB and TNF-alpha-TRAF2-NF-κB signaling / 中国药理学与毒理学杂志

OBJECTIVE This study was to investigate the effects of CP- 25 on the functions of activated human B cells through regulating BAFF and TNF-alpha signaling. METHODS B cells from peripheral blood mononuclear cells (PBMCs) of normal human were isolated using magnetic cell separation (MACS) by a positive selection. B cells (107 cells·mL-1) were stimulated by BAFF (100 ng·mL-1) or TNF-alpha (100 ng·mL-1) for two hours, and then were treated with CP-25 (10-5 mol·L-1) or Rituximab (5 μg·mL-1) or Etanercept (10 μg·mL-1). B cell proliferation was detected by CCK-8. B cell subsets and BAFF receptors (BAFFR, BCMA and TACI) were analyzed by flow cytometry. The expression of TNFR1 and TNFR2 on B cells was analyzed by flow cytometry. The expression of MKK3, MKK6, P-p38, P-p65, TRAF2 and p100/52 was analyzed by Western blotting. RESULTS CP-25 inhibited B cells proliferation stimulated by BAFF or TNF- alpha. CP- 25, Rituximab and Etanercept reduced the percentage and numbers of CD19+ B cells, CD19+CD20+ B cells, CD19+CD27+ B cells and CD19+CD20+CD27+ B cells induced by BAFF or TNF-alpha. CP-25 down-regulated the high expression of BAFFR, BCMA and TACI stimulated by BAFF or TNF-alpha. CP-25, Rituximab and Etanercept down-regulated significantly the expression of TNFR1 and TNFR2 on B cell stimulated by BAFF or TNF-alpha. CP-25, Rituximab and Etanercept down-regulated the expression of MKK3, P-p38, P-p65, TRAF2 and p52 in B cells stimulated by BAFF and the expression of TRAF2 and P- p65 in B cells stimulated by TNF-alpha. CONCLUSION CP- 25 regulated moderately activated B cells function by by regulating the classical and alternative NF-κB signaling pathway mediated by BAFF and TNF-alpha-TRAF2-NF-κB signaling pathway. This study suggests that CP-25 may be a promising anti-inflammatory immune and soft regulation drug.