Müller-Ladner U, Judex M, Ballhorn W, Kullmann F, Distler O, Schlottmann K, Gay R E, Schölmerich J, Gay S
Department of Internal Medicine I, University of Regensburg, Regensburg, Germany.
J Immunol. 2000 Apr 1;164(7):3894-901. doi: 10.4049/jimmunol.164.7.3894.
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 transcription in the nucleus. We examined the expression and activation of IL-4 STAT and its related kinase Jak-1 in rheumatoid synovium. Rheumatoid arthritis (RA) synovial frozen sections of patients with short-term (<1 year) and long-term disease (>2 years) were examined using in situ hybridization and immunohistochemistry. IL-4 STAT mRNA could be detected in synovium of patients 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 synovial lining, both fibroblasts and macrophages expressed IL-4 STAT mRNA. IL-4 STAT and Jak-1 protein was expressed by synoviocytes, and up-regulation could be induced after stimulation with IL-4. Activation of IL-4 STAT was reflected by phosphorylation of IL-4 STAT. The results indicate that IL-4 STAT is involved in key pathomechanisms in RA synovium and that IL-4 STAT-dependent pathways operate in early and late stages of the disease and presumably contribute to inhibitory immune mechanisms in RA synovium.
信号转导和转录激活因子（STATs）在信号分子与其受体结合后作为第二信使发挥作用。IL-4 STAT直接参与细胞核中依赖IL-4的基因转录。我们研究了类风湿滑膜中IL-4 STAT及其相关激酶Jak-1的表达和激活情况。使用原位杂交和免疫组织化学方法检测了短期（<1年）和长期疾病（>2年）患者的类风湿关节炎（RA）滑膜冰冻切片。在短期和长期RA患者的滑膜中均可检测到IL-4 STAT mRNA。在滤泡性炎性浸润中可见IL-4 STAT mRNA的最强表达。在滑膜衬里中，成纤维细胞和巨噬细胞均表达IL-4 STAT mRNA。滑膜细胞表达IL-4 STAT和Jak-1蛋白，用IL-4刺激后可诱导其上调。IL-4 STAT的激活通过IL-4 STAT的磷酸化来反映。结果表明，IL-4 STAT参与了RA滑膜的关键发病机制，且依赖IL-4 STAT的途径在疾病的早期和晚期均发挥作用，可能有助于RA滑膜中的免疫抑制机制。
