The Influence Of Paeoniflorin And Recombinant Human Type Ⅱ Tumor Necrosis Factor Receptor-antibody Fusion Protein On Human Synovial Cells And Part Mechanism

Objective Rheumatoid arthritis (RA) is a systemic autoimmune disease that primarilytargets the synovial membrane, cartilage, and bone. tumor necrosis factor-α (TNF-α)play an important role in the inflammatory and autoimmune disease. The recombinanthuman tumor necrosis factor-alpha receptor II:IgG Fc (rhTNFR:Fc), a recombinantfusion protein that binds and neutralizes TNF-α, has been shown therapeutic effectson RA. To investigate the regulatory effects of rhTNFR: Fc and paeoniflorin (Pae)combination therapy on TNF-α stimulated human fibroblast-like synoiocyte (FLS)proliferation via TNFR signaling pathway.Methods Informed consent, we collect normal synovial tissue of patients with hiparthroplasty, and cultured human FLS with tissue block method. Take the threegenerations of synovial cells, and then given Pae (10-5,10-6,10-7,10-8,10-9mol/L) andrhTNFR:Fc (100,10,1,0.1,0.01mg/L) and combination therapy. Proliferations ofhuman FLS activated by TNF-α was detected by MTT method, and tumor necrosisfactor receptor (TNFR1), TNF-associated factor-2(TRAF2), TNF receptor associateddeath domain protein (TRADD) expression in FLS was detected by Semi-quantitativeanalysis of the immunohistochemical method.Results1Effects of rhTNFR:Fc or Pae or combination therapy on the TNF-α-induced proliferation of FLS in vitroThe three generations of human FLS was removed under sterile conditions. Theproliferation experiments show that the Pae(10-5mol/L) and rhTNFR: Fc(10mg/L)combination therapy groups on the efficacy of the FLS proliferation are better thanthe drug alone group.2Effects of rhTNFR:Fc or Pae or combination therapy on the TNFR1、TRAF2and TRADD expression of FLS in vitroThe three generations of human FLS was removed under sterile conditions.Immunohistochemical experiments showed that Pae(10-5mol/L) and rhTNFR: Fc (10mg/L) both can downregulate the TNFR1and TRAF2expression, and upregulateTRADD expression in FLS.Conclusion1Pae and rhTNFR: Fc combination therapy on the efficacy of the FLS proliferation issuperior to monotherapy.2Pae and rhTNFR: Fc both can downregulate the TNFR1and TRAF2expression,and upregulate TRADD expression in FLS. And it is may be he mechanism of Paesuppression influence on FLS3The mechanism of their influence on FLS may be achieved by regulating theTRADD and TRAF2.