They recognize “pathogen-associated molecular patterns ” which are structurally conserved molecules derived from microbes and are distinguishable from host molecules, and activate the innate immune responses. Till now, more than 13 members of the TLR family have been identified in mammals. To define the expression profile of TLRs and their pathogenic roles will improve our understanding of RA. In this study, we systemically detected the expression of TLRs in RA, and revealed their roles in perpetuating the persistent inflammation. In this study, we revealed the distinct expression pattern of TLRs in RA. These receptors, particularly TLR2, TLR3, and TLR4 played crucial roles in the production of inflammatory cytokines, MMPs, and VEGF by RASF. More important, ligation of these TLRs expressed by RASF promoted inflammatory Th1 and Th17 responses. Thus TLRs contribute not only to the initiation but also to the perpetuation of the inflammation in RA which would be served as new therapeutic targets for the disease. One of the most significant characteristics of RA is the intensive inflammation that is out of control. Managing to control the inflammation could prevent the Oxysophocarpine disease progression, which would be the optimal strategy for RA therapy. One direct strategy is targeting the pathogenic inflammatory cytokines. Indeed, inhibitors of TNF-a have greatly advanced the management of RA, dramatically decreasing signs and symptoms of the diseases. At present, at least three agents are available which differ in pharmacokinetics and ability to bind lymphotoxin, crosslink membrane-bound TNF and induce apoptosis. Recently, IL-6 has also been proved to be a therapeutic target for RA. IL-6R monoclonal antibody 
tocilizumab showed promising perspective in treating RA patients. Biological reagents targeting other inflammatory cytokines would appear in the following studies. However, RA is a complicated disease involving many inflammatory cytokines. So, targeting the upstream sources of the inflammation would demonstrate better efficacy for RA therapy. Nonetheless, how the inflammation in RA is initiated, propagated, and maintained remains controversial. Infection has long been speculated to be an underlying factor contributing to RA pathogenesis. Indeed, peptidoglycan, bacterial and viral DNA as well as viral RNA were proved to be present in RA patient inflamed joints. These PAMPs would activate the corresponding TLRs, inducing robust inflammatory mediator production. In addition, endogenous heat shock protein, fibrinogen, hyaluronan, and double stranded RNA from apoptotic cells also exist in RA joints. These “danger-associated molecular patterns ” could also provoke TLRs to induce inflammation. In this study, we proved that peptidoglycan, ploy, LPS, and CpGcould activate RASF to induce vigorous inflammatory mediator production. This suggests that TLRs serve as an important contributor to the initiation and propagation of the inflammatory responses in RASF, which would eventually exacerbate the inflammation in RA. In addition, in the current study, we showed for the first time that TLR activation exacerbated RASF-mediated inflammatory Th1 and Th17 responses. Th1 cells are considered to be the conventional pathogenic cells in RA, because RA is thought to be a Th1-biased disease with Th1/Th2 imbalance. Recently, attention has increasingly focused on the role of Th17 cells, a subset that produces IL-17A, 17F, 21, and 22 and TNF-a. IL17A, which Clofentezine synergizes with TNF-a.