A novel mechanism for TNF-alpha regulation by p38 MAPK: involvement of NF-kappa B with implications for therapy in rheumatoid arthritis.

摘要: TNF-alpha is a key factor in variety of inflammatory diseases. This study examines the role p38 MAPK regulation primary human cells relevant to inflammation, e.g., macrophages and rheumatoid synovial cells. Using dominant negative variant (D168A) kinase inhibitor, SB203580, we confirm that regulates production using posttranscriptional mechanism requiring 3' untranslated region gene. However, LPS-activated also detect second previously unidentified mechanism, modulation transcription. mediated through NF-kappaB. Interestingly this was not observed Importantly however, mutant MAPK, but SB203580 effective at inhibiting spontaneous these ex vivo cell cultures. These data indicate there are potential major differences signaling have bearing on use as target for therapy. results despite disappointing with inhibitors clinic, valid disease.