p38 Mitogen-activated protein kinase and c-Jun-NH2-terminal kinase regulate interleukin-8 and RANTES production in hyperosmolarity stimulated human bronchial epithelial cells
p38 Mitogen-activated protein kinase and c-Jun-NH2-terminal kinase regulate interleukin-8 and RANTES production in hyperosmolarity stimulated human bronchial epithelial cells
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DOI：
10.1046/j.1440-1843.2002.00401.x
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发表时间：
2002-09-01
期刊：
影响因子：
6.9
通讯作者：
Horie, T
中科院分区：
文献类型：
--
作者：
Furuichi, S;Hashimoto, S;Horie, T
目的：我们以前已经表明，p38丝裂原活化蛋白激酶（MAPK）调节，至少部分，高渗诱导的白细胞介素（IL）-8在人支气管上皮细胞（BEC）的表达。在先前的研究中，高渗也激活c-Jun-NH 2-末端激酶（JNK）;然而，JNK信号通路的作用尚未确定。在本研究中，我们使用JNK信号通路的新型抑制剂CEP 11004来研究JNK信号通路在高渗诱导的BEC产生IL-8和RANTES中的作用，以澄清这些问题。已与SB 203580预孵育的支气管上皮细胞，将CEP 11004或其组合暴露于高渗培养基中，然后测定这些细胞中p38 MAPK和JNK磷酸化活性以及培养上清液中IL-8和RANTES浓度。高渗可诱导p38 MAPK和JNK的苏氨酸和酪氨酸磷酸化，SB 203580和CEP 11004分别抑制p38 MAPK和JNK的活性，SB 203580和CEP 11004部分抑制IL-8和RANTES的产生，PD 98059则无此作用;结论：p38 MAPK和JNK信号通路参与了高渗诱导BEC产生IL-8和RANTES的调节。
Objective: We have previously shown that p38 mitogen-activated protein kinase (MAPK) regulates, at least in part, hyperosmolarity induced interleukin (IL)-8 expression in human bronchial epithelial cells (BEC). In the previous study, hyperosmolarity also activated c-Jun-NH2-terminal kinase (JNK); however, the role of the JNK signalling pathway has not been determined. In the present study, we examined the role of the JNK signalling pathway in hyperosmolarity induced IL-8 and RANTES production by BEC using the novel inhibitor of the JNK signalling pathway CEP 11004 in order to clarify these issues.Methods: Bronchial epithelial cells that had been pre-incubated with SB 203580, CEP 11004 or a combination of these were exposed to a hyperosmolar medium and then the p38 MAPK and JNK phosphorylation activity in these cells and IL-8 and RANTES concentrations in the culture supernatants were determined.Results: The results showed that: (i) hyperosmolarity induced the threonine and tyrosine phosphorylation of p38 MAPK and JNK; (ii) SB 203580, as the specific inhibitor of p38 MAPK activity, and CEP 11004 attenuated hyperosmolarity induced p38 MAPK and JNK activity, respectively; (iii) SB 203580 and CEP 11004, but not PD 98059, partially attenuated IL-8 and RANTES production; and (iv) a combination of SB 203580 and CEP 11004 attenuated IL-8 and RANTES production in an additive fashion.Conclusion: These results indicate that p38 MAPK and the JNK pathway regulate hyperosmolarity induced IL-8 and RANTES production by BEC.