%0 Journal Article %A Qingquan Chen %A Bruno Casali %A Laura Pattacini %A Luigi Boiardi %A Carlo Salvarani %T Tumor necrosis factor-alpha protects synovial cells from nitric oxide induced apoptosis through phosphoinositide 3-kinase Akt signal transduction. %D 2006 %J The Journal of Rheumatology %P 1061-1068 %V 33 %N 6 %X OBJECTIVE: To investigate the anti-apoptotic role of tumor necrosis factor-a (TNF-a) and its signaling pathways in cultured human fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis. METHODS: FLS were cultured in Dulbecco's modified Eagle's medium. Apoptotic cells were identified by TUNEL assay and Hoechst staining. Cell viability was determined by the MTT method. Expression of phospho-Akt and phospho-BAD was measured by Western blotting. RESULTS: A 24-h TNF-a treatment prevented FLS apoptosis induced by nitric oxide (NO) donor sodium nitroprusside dihydrate (SNP), achieving 70% protection. At 1-10 ng x ml-1 concentrations, TNF-a induced phosphorylation of Akt and BAD in a time and concentration-dependent manner. This effect was blocked by treatment with both LY294002 and nuclear factor-kB inhibitor pyrrolidine-dithiocarbamate. CONCLUSION: TNF-a has an anti-apoptotic effect in human FLS. Activation of Akt and BAD may have an important role in this process. %U https://www.jrheum.org/content/jrheum/33/6/1061.full.pdf