Matsumiya Tomoh, Imaizumi Tadaatsu, Itaya Hiroyuki, Shibata Takeo, Yoshida Hidemi, Sakaki Hirotaka, Kimura Hiroto, Satoh Kei
Department of Dentistry and Oral Surgery, Hirosaki University School of Medicine,Hirosaki 036-8562, Japan.
Life Sci. 2002 May 17;70(26):3179-90. doi: 10.1016/s0024-3205(02)01560-6.
Growth-related oncogene protein-alpha (GRO-alpha) is a member of the C-X-C chemokine family with a wide variety of biological activities. We studied the production of GRO-alpha by human umbilical vein endothelial cells (HUVEC) in response to the stimulation with soluble form of interleukin-6 receptor alpha (sIL-6R). sIL-6R stimulated HUVEC to express GRO-alpha mRNA and secrete GRO-alpha protein in concentration-and time-dependent manners. The sIL-6R-induced GRO-alpha expression was inhibited by the pretreatment of the cells with AG490, a janus kinase 2 (JAK2) inhibitor, or with U0126, a MAP kinase-ERK kinase (MEK) inhibitor. sIL-6R also induced the phosphorylation of both Src homology 2-protein tyrosine phosphatase-2 (SHP-2), signal transducer and activator of transcription 3 (STAT3) and MEK. AG490 pretreatment inhibited the MEK phosphorylation but did not affect the STAT3 phosphorylation. We conclude that sIL-6R induces GRO-alpha expression in HUVEC through the activation of JAK2 and MEK.
生长相关癌基因蛋白α（GRO-α）是C-X-C趋化因子家族的成员，具有多种生物学活性。我们研究了人脐静脉内皮细胞（HUVEC）在可溶性白细胞介素-6受体α（sIL-6R）刺激下GRO-α的产生。sIL-6R以浓度和时间依赖性方式刺激HUVEC表达GRO-α mRNA并分泌GRO-α蛋白。用janus激酶2（JAK2）抑制剂AG490或丝裂原活化蛋白激酶-细胞外信号调节激酶激酶（MEK）抑制剂U0126预处理细胞可抑制sIL-6R诱导的GRO-α表达。sIL-6R还诱导Src同源2-蛋白酪氨酸磷酸酶-2（SHP-2）、信号转导子和转录激活子3（STAT3）以及MEK的磷酸化。AG490预处理可抑制MEK磷酸化，但不影响STAT3磷酸化。我们得出结论，sIL-6R通过激活JAK2和MEK诱导HUVEC中GRO-α的表达。
