p38丝裂原活化蛋白激酶调节人支气管上皮细胞由肿瘤坏死因子α、白细胞介素-1α和血小板活化因子诱导的调节激活正常T细胞表达和分泌的因子及粒细胞巨噬细胞集落刺激因子的产生。

p38 MAP kinase regulates TNF alpha-, IL-1 alpha- and PAF-induced RANTES and GM-CSF production by human bronchial epithelial cells.

作者信息

Hashimoto S, Matsumoto K, Gon Y, Maruoka S, Kujime K, Hayashi S, Takeshita I, Horie T

机构信息

First Department of Internal Medicine, Nihon University School of Medicine, Itabashi-Ku, Tokyo, Japan.

出版信息

Clin Exp Allergy. 2000 Jan;30(1):48-55. doi: 10.1046/j.1365-2222.2000.00641.x.

DOI:10.1046/j.1365-2222.2000.00641.x

PMID:10606930

Abstract

BACKGROUND

RANTES and granulocyte macrophage-colony stimulating factor (GM-CSF) play an important role in the production of allergic inflammation of the airway through their chemotactic activity for eosinophils. Recent studies have indicated that p38 mitogen-activated protein (MAP) kinase regulates cytokine expression in various cells; however, the role of p38 MAP kinase in RANTES and GM-CSF production in human bronchial epithelial cells (BECs) has not yet been determined.

OBJECTIVE

In the present study, we examined serine phosphorylation of MKK3 and MKK6 which is the upstream regulator of p38 MAP kinase and p38 MAP kinase activation in tumour necrosis factor (TNF)-alpha, interleukin (IL)-1 alpha and platelet-activating factor (PAF)-stimulated BECs and the effect of SB 203580 as the specific inhibitor for p38 MAP kinase activity on RANTES and GM-CSF expression in order to clarify the intracellular signal regulating RANTES and GM-CSF production by human BECs.

RESULTS

The results showed that TNF alpha, IL-1 alpha and PAF induced serine phosphorylation of MKK3 and MKK6, and p38 MAP kinase activation in BECs. SB 203580 inhibited p38 MAP kinase activity and RANTES and GM-CSF production by TNF alpha-, IL-1 alpha- or PAF-stimulated human BECs.

CONCLUSIONS

These results indicate that p38 MAP kinase plays an important role in TNF alpha-, IL-1 alpha- or PAF-activated signalling pathway which regulates RANTES and GM-CSF production by BECs and that the specific inhibitor for p38 MAP kinase activity might be useful for the treatment of allergic inflammation of the airway.

摘要

背景

调节激活正常T细胞表达和分泌的趋化因子（RANTES）和粒细胞巨噬细胞集落刺激因子（GM-CSF）通过其对嗜酸性粒细胞的趋化活性在气道过敏性炎症的产生中起重要作用。最近的研究表明，p38丝裂原活化蛋白（MAP）激酶调节各种细胞中的细胞因子表达；然而，p38 MAP激酶在人支气管上皮细胞（BECs）中RANTES和GM-CSF产生中的作用尚未确定。

目的

在本研究中，我们检测了肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1α和血小板活化因子（PAF）刺激的BECs中p38 MAP激酶的上游调节因子MKK3和MKK6的丝氨酸磷酸化以及p38 MAP激酶的激活情况，以及p38 MAP激酶活性的特异性抑制剂SB 203580对RANTES和GM-CSF表达的影响，以阐明调节人BECs产生RANTES和GM-CSF的细胞内信号。