Bhat G J, Raghu G, Gunaje J J, Idell S
Department of Specialty Care Services, University of Texas Health Center at Tyler, 11937 US Hwy 271, Tyler, Texas, 75701, USA.
Biochem Biophys Res Commun. 1999 Mar 24;256(3):626-30. doi: 10.1006/bbrc.1999.0381.
Exposure of primary human lung fibroblasts (HLF) to interleukin-6 (IL-6) rapidly induced Stat3 (signal transducers and activators of transcription 3) tyrosine phosphorylation. In these cells, alpha-thrombin did not induce tyrosine phosphorylation of Stat3; however, it potently induced its serine phosphorylation. Interestingly, a short pretreatment of cells with alpha-thrombin significantly inhibited IL-6-induced tyrosine phosphorylation of Stat3. The inhibition by alpha-thrombin was attenuated if cells were pretreated with U0126, a specific inhibitor of the mitogen-activated protein (MAP) kinase kinase 1 (MAPKK1). Exposure of HLF cells to IL-6 induced a twofold increase in gp130 mRNA levels; however, alpha-thrombin inhibited this IL-6-induced response almost to control levels. These results demonstrate, for the first time, that in HLF cells alpha-thrombin inhibits IL-6-induced Stat3 signaling via activation of MAPKK1 and that this cross-talk regulates IL-6-induced gp130 gene expression.
将原代人肺成纤维细胞（HLF）暴露于白细胞介素-6（IL-6）中可迅速诱导信号转导与转录激活因子3（Stat3）的酪氨酸磷酸化。在这些细胞中，α-凝血酶不会诱导Stat3的酪氨酸磷酸化；然而，它能有效诱导其丝氨酸磷酸化。有趣的是，用α-凝血酶对细胞进行短暂预处理可显著抑制IL-6诱导的Stat3酪氨酸磷酸化。如果用丝裂原活化蛋白（MAP）激酶激酶1（MAPKK1）的特异性抑制剂U0126对细胞进行预处理，α-凝血酶的抑制作用会减弱。将HLF细胞暴露于IL-6会使gp130 mRNA水平增加两倍；然而，α-凝血酶几乎将这种IL-6诱导的反应抑制到对照水平。这些结果首次证明，在HLF细胞中，α-凝血酶通过激活MAPKK1抑制IL-6诱导的Stat3信号传导，并且这种相互作用调节IL-6诱导的gp130基因表达。
