Although a similar trend was observed with the decoy receptor TRAIL R3 the differences were not as marked. The other decoy receptor, TRAIL R4, was expressed Ivacaftor molecular weight in synovial Inhibitors,Modulators,Libraries tissues Inhibitors,Modulators,Libraries from all forms of arthritis and, to a lesser extent, in normal synovial tissues. TRAIL R4 was expressed predominantly in the synovial lining and appeared to be associated with the nuclear and perinu clear regions of cells, consistent with a previous report. Statistical analysis for SQAs of all immunohistochemical label ling and TUNEL results is presented in Table 2. Apoptosis detection The TUNEL method identified many apoptotic cells in inactive RA synovium but very few apoptotic cells were seen in active RA and normal synovia. This difference was statisti cally significant.

Conversely, Inhibitors,Modulators,Libraries fewer cells expressing cleaved caspase 3 were observed in inactive RA but there were many cells expressing cleaved caspase Inhibitors,Modulators,Libraries 3 in active RA and SpA synovia. The difference between active and inactive RA was statistically significant. Cleaved caspase 8 was only weakly detected in the synovial tissues both from active RA and inactive RA patients. Survivin and xIAP expression Both xIAP and survivin were highly expressed in the cytoplasm of cells in synovial tissue from active RA. xIAP was expressed at significantly higher levels in active RA compared with normal synovial tissue. In addition, sur vivin was expressed at significantly higher levels in synovial tis sue from patients with active RA compared with other types of synovial tissue tested.

Dual label ling of this tissue for cleaved caspase 3 and xIAP demon strated that many, but not all, cells expressing xIAP also expressed cleaved caspase 3. Cells expressing TRAIL and TRAIL receptors Inhibitors,Modulators,Libraries Double labelling was carried out to determine the phenotype of cells expressing TRAIL and TRAIL receptors R1 and R4. CD68 positive cells present in the synovial lining levels selleck chemical of caspase 3 mRNA expression in normal synovia and active RA revealed similar levels of expression, while there was a trend towards reduced caspase 3 expression with inactive RA, although this difference was not shown to be significant. A similar pattern was found with survivin mRNA expression to that of caspase 3. There was a similar level of expression between normal synovia and active RA, however, survivin mRNA was expressed at significantly lower levels in inactive RA compared with active RA. xIAP mRNA expression was found to be highest in normal syn ovia compared with inactive and active RA, however, this expression was found to be quite variable within the samples investigated. In addition, a trend towards higher xIAP mRNA expression in active RA compared with inactive RA was also found, although a significant difference was not observed.