Correlation between CTGF and certainly diseases activity Serum CTGF levels were compared between the patients hav ing high and low RA disease activities and the effect of infliximab on the serum levels of CTGF was examined in RA patients. We could not fully obtain informa tion of articular manifestations with these patients, therefore, the patients were provisionally divided into two groups, active inactive RA, depending upon the serum level of CRP. Other comparative parameters such as erythrocyte sedimentation rate, white blood cell, and matrix metallopro tease 3 were also significantly elevated in the active RA group. As shown in Figure 1B, the levels of serum CTGF were significantly elevated in active RA compared with inactive RA.

Interestingly, the frequency of sera with elevated CTGF levels designed as above the cut off points was signifi cantly greater in the active RA group than the inactive RA group. Figure 1C shows a reduction of serum CTGF levels in response to infliximab treat ment. The statistical reduction of serum CTGF levels was observed after infliximab Inhibitors,Modulators,Libraries treatement. These data suggest that serum levels of CTGF correlate with the disease activity and concern a pathogenesis of RA. Effects of TNF for the production of CTGF from synovial fibroblasts or chondrocytes To investigate the CTGF contribution for pathogenesis of RA, the CTGF expression was evaluated by immunohistochemical analysis in synovial tissues of surgical samples from the knee joint of RA patients and OA patients as a disease control. An inflamed synovial tissue was recognized in samples from RA compared Inhibitors,Modulators,Libraries to OA in HE staining.

A strong expres sion of CTGF was observed in inflamed synovial tissue with RA, and none or very weak expression was recognized in sam ples with OA. Inflamed synovial tissue of RA gen erally consists of fibroblasts and lineage of hemapoietic cells such as macrophage, neutrophils, and lymphocytes. To inves tigate a more specific production Inhibitors,Modulators,Libraries site of CTGF, the samples were also stained by anti F4 80 antibody, which is generally used for a specific marker of macrophages. As Inhibitors,Modulators,Libraries expected, a significant infiltration of macrophages was observed in Inhibitors,Modulators,Libraries RA compared to OA. Double staining using anti CTGF antibody and anti F4 80 antibody showed that expres sion of CTGF and F4 80 was not overlapped, sug gesting that these molecules were produced at different sites.

Because it has been reported that CTGF was not generally expressed in hemopoietic lineage cells, we considered that CTGF was mainly produced at synovial fibroblasts in inflamed synovial tissues with RA rather than hemopoietic cells like macrophages. In order to investigate http://www.selleckchem.com/products/kpt-330.html how TNF regulates the production of CTGF in synovial fibroblasts, CTGF expression was measured in MH7A cells stimulated with or without recombinant TNF .