Activation of the IL-4 STAT pathway in rheumatoid synovium

STATs act as second messenger after binding of a signaling molecule to its receptor. IL-4 STAT is directly involved in the Il-4-dependent gene transcr iption in the nucleus. We examined the expression and activation of IL-4 ST AT and its related kinase Jak-1 in rheumatoid synovium, Rheumatoid arthriti s (RA) synovial frozen sections of patients with short-term (<1 year) and l ong-term disease (>2 years) were examined using in situ hybridization and i mmunohistochemistry. IL-4 STAT mRNA could be detected in synovium of patien ts with short-term and long-term RA, The most intensive expression of IL-4 STAT mRNA could be seen in follicular inflammatory infiltrates, In the syno vial lining, both fibroblasts and macrophages expressed IL-4 STAT mRNA. IL- 4 STAT and Jak-1 protein was expressed by synoviocytes, and up-regulation c ould be induced after stimulation with IL-4. Activation of IL-4 STAT was re flected by phosphorylation of IL-4 STAT. The results indicate that IL-4 STA T is involved in key pathomechanisms in RA synovium and that IL-4 STAT-depe ndent pathways operate in early and late stages of the disease and presumab ly contribute to inhibitory immune mechanisms in RA synovium.