Interleukin-1beta induces MUC2 and MUC5AC synthesis through cyclooxygenase-2 in NCI-H292 cells.
Interleukin-1beta induces MUC2 and MUC5AC synthesis through cyclooxygenase-2 in NCI-H292 cells.
复制标题
Interleukin-1beta 通过 cyclooxygenase-2 在 NCI-H292 细胞中诱导 MUC2 和 MUC5AC 合成。
作者：
Yong;E. Kwon;D. Park;Si;S. Yoon;S. Baek
白细胞介素-1 β（IL-1 β）与气道炎性疾病的发病机制有关。在本研究中，我们研究了MUC 2和MUC 5AC表达的调节及其通过环氧化酶-2（考克斯-2）和前列腺素E（2）（PGE（2））的调节机制。经IL-1 β激活的细胞在mRNA和蛋白水平均显示考克斯-2、MUC 2和MUC 5AC表达增加。选择性考克斯-2抑制剂NS 398可阻断粘蛋白的产生，PGE（2）可直接诱导MUC 2和MUC 5AC在mRNA和蛋白水平上的表达，并呈剂量依赖性。这些结果表明PGE（2）在IL-1 β诱导的NCI-H292细胞粘蛋白合成中发挥作用。为了研究考克斯-2上游分子在粘蛋白调节中的作用，我们检测了丝裂原活化蛋白激酶（MAPK）的作用。IL-1 β激活的细胞显示细胞外信号调节激酶（ERK）1/2和p38磷酸化增加，IL-1 β诱导的MUC 2和MUC 5AC产生被ERK通路抑制剂PD 98059或p38抑制剂SB 203580阻断。两种MAPK的抑制都减少了IL-1 β诱导的考克斯-2表达和PGE（2）合成。此外，向细胞中加入PGE（2）克服了两种MAPK抑制剂对IL-1 β诱导的粘蛋白产生的抑制作用。这些结果表明，在人肺上皮细胞中，IL-1 β激活ERK或p38以诱导考克斯-2的产生，这反过来又诱导MUC 2和MUC 5AC的产生。
Interleukin-1beta (IL-1beta) has been implicated in the pathogenesis of inflammatory diseases of the airway. In this study, we investigated the regulation of MUC2 and MUC5AC expression and of their regulatory mechanisms through cyclooxygenase-2 (COX-2) and prostaglandin E(2) (PGE(2)). Cells activated by IL-1beta showed increased COX-2, MUC2, and MUC5AC expressions at both the mRNA and protein levels. Mucin production was blocked by the selective COX-2 inhibitor NS398, and PGE(2) directly induced MUC2 and MUC5AC expression at both the mRNA and protein levels in a dose-dependent manner. These results suggest a role for PGE(2) in IL-1beta-induced mucin synthesis in NCI-H292 cells. To investigate the roles of molecules upstream of COX-2 in mucin regulation, we examined the role of mitogen-activated protein kinases (MAPKs). Cells activated by IL-1beta showed increased extracellular signal-regulated kinase (ERK)1/2 and p38 phosphorylation, and IL-1beta-induced MUC2 and MUC5AC production was blocked by the ERK pathway inhibitor PD98059 or the p38 inhibitor SB203580. The inhibition of both MAPKs reduced IL-1beta-induced COX-2 expression and PGE(2) synthesis. Furthermore, the addition of PGE(2) to cells overcame the inhibitory effects of both MAPK inhibitors in IL-1beta-induced mucin production. These results indicate that in human pulmonary epithelial cells, IL-1beta activates ERK or p38 to induce COX-2 production, which in turn induces MUC2 and MUC5AC production.
登录
查看更多内容
DOI：
10.1073/pnas.95.10.5718
发表时间：
1998-05-12
影响因子：
11.1
作者：
Li, JD;Feng, WJ;Basbaum, C
通讯作者：
Basbaum, C
DOI：
10.1073/pnas.96.6.3081
发表时间：
1999-03-16
影响因子：
11.1
作者：
Takeyama, K;Dabbagh, K;Nadel, JA
通讯作者：
Nadel, JA
影响因子：
15.9
作者：
Longphre, M;Li, D;Basbaum, C
通讯作者：
Basbaum, C
影响因子：
15.9
作者：
Tilley, SL;Coffman, TM;Koller, BH
通讯作者：
Koller, BH
DOI：
10.1164/ajrccm.160.supplement_1.12
发表时间：
1999-11-01
影响因子：
24.7
作者：
Basbaum, C;Lemjabbar, H;McNamara, N
通讯作者：
McNamara, N