High IL-17A levels have been observed in patients with autoimmune diseases such as RA [123].

Previous studies have reported that IL-17A stimulation leads to TRAF 6 recruitment to the IL17RA-IL17RC receptor heterodimer complex, and induces NFκB activation [121]. Recent reports have shown that IL-17E (IL-25) and IL-17B have an affinity for IL17RB [121] and [124]. IL-17E signaling through the IL-17RA-IL17RB receptor heterodimer complex induces Th2 responses by activating the MAPK and NFκB pathways. IL-17E is produced by eosinophils, mast cells and airway epithelial cells and stimulates asthma-like, allergic inflammation [121] and [125]. On the other hand, IL-17B, which is expressed in chondrocytes [126], has been shown to interact with IL-17RB [121]; ZD6474 ic50 however, its biological function remains unclear. The IL-17 cytokine family, derived from a wide array of cell types, coupled to the differential expression of their receptors on various cells and tissues, illustrate the complexity of the cytokine family network in modulating the immune response and inflammation.

Further studies into the role of IL17RB in joint diseases such as RA and OA remain necessary. We have reported several IL-1β-responsive genes other than the top 10 selleck chemicals llc genes up-regulated in FLS by IL-1β- and/or TNF-α. The expression and the production of monocyte colony stimulating factor (M-CSF), also known as CSF1, which was ranked 26 with IL-1β-stimulation and was ranked 22 with TNF-α-stimulation (data not shown), was increased in FLS treated with IL-1β (Fig. 6), and was detected in the synovial tissues of the IL-1β-injected TMJ in rats [127]. M-CSF is critical for the proliferation and survival of macrophages and osteoclast precursors [128] and [129]. In contrast, gene expressions FER of inhibitor κBα (IκBα), TNF-α-induced protein 3, (TNFAIP3,

also known as A20), TNFAIP3-interacting protein 1 (TNIP1, also known as ABIN1; A20-binding inhibitor of NFκB1), and cellular inhibitors of apoptosis (c-IAP, also known as BIRC; baculoviral IAP repeat-containing protein), which inhibit NFκB activation, were also increased after IL-1β treatment in FLS (Fig. 7) [130]. IκBα was ranked 64 with IL-1β-stimulation and ranked 42 with TNF-α-stimulation. TNFAIP3 was ranked 27 with IL-1β-stimulation and ranked 19 with TNF-α-stimulation. TNIP1 was ranked 78 with IL-1β-stimulation and ranked 55 with TNF-α-stimulation. c-IAP2 was ranked 25 with IL-1β-stimulation and ranked 28 with TNF-α-stimulation. The gene expression of these inhibitors of NFκB activation was rapidly induced by NFκB in a negative feedback loop that may maintain a transient NFκB response. This review focused on the molecules that are enhanced in FLS treated with IL-1β and/or TNF-α based on microarray analysis, and summarized their functions based on recent studies.