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**9** 

*Japan* 

**Profiling Inflammatory Genes** 

Yasuko Shibata and Yoshimitsu Abiko *Department of Biochemistry and Molecular Biology Nihon University School of Dentistry at Matsudo* 

**and Signaling Pathways in Rheumatoid** 

Rheumatoid arthritis (RA) is an autoimmune joint disease characterized by inflammation and destruction of the articular surfaces and bone. During joint movement, synovial tissues contribute to mechanical load bearing by changing their shape. These elastic synovial membranes are an early target of rheumatic inflammation, and together with chondrocytes, become a primary source of inflammatory factors (e.g., cytokines) that enter the synovial fluid (Dayer, 2004, Firestein, 2007). The pathophysiological steps leading to RA include inflammation, proliferation of synovial cells, and attachment to and invasion of adjacent cartilage and bone by fibroblast-like cells derived from rheumatoid synoviocytes (RA-FLSs)

In the healthy synovium, one to three layers of synoviocytes, the macrophage-like type A and the more abundant fibroblast-like type B (also referred to as synovial fibroblasts), form the synovial lining layer separating the synovial sublining layer of loose connective tissue from the joint cavity (Iwanaga et al., 2000). The joint damage observed in RA is mainly mediated by macrophage/macrophage-like cell-derived cytokines, such as interleukin (IL)- 1, IL-6 and tumor necrosis factor (TNF)-, which induce neutral protease production by FLSs and articular chondrocytes (Houssiau et al., 1988, Feldmann & Maini, 1999, Dayer, 2002). Although IL-1 and TNF- share many biological activities that are relevant in RA, early studies of experimental arthritis models have demonstrated that IL-1 plays a predominant role in cartilage destruction via inflammatory processes that include the activation of matrix metalloproteinases (MMPs) (Borghaei et al., 1998) and the inhibition of the synthesis of extracellular matrix (ECM) molecules (Mauviel et al., 1988). In particular, IL-1 is readily detected, long after the onset of RA, at high levels in the synovial fluid of RA patients. IL-1 can significantly alter the expression of a variety of genes, including inflammatory mediators such as cytokines and MMPs (Sun & Yokota, 2002, Suzuki et al., 2010). In addition, IL-1 stimulates bone resorption by activating osteoclasts (Goldring, 2003). That said, there is little comprehensive information available on the effects of IL-1 on

RA-FLSs not only mediate tissue destruction, but also are considered to play a major role in initiating and driving RA in concert with inflammatory cells (Huber, 2006, Bartok &

(Firestein, 1996, Pap et al., 2000, Tolboom et al., 2005, Bartok & Firestein, 2010).

**1. Introduction** 

fibroblast-like synoviocytes (FLSs).

**Synoviocytes for RA Light Therapy** 

