Muc5ac Gene Expression Induced by Cigarette Smoke is Mediated Via a Pathway Involving ERK1/2 and p38 MAPK

被引：0

作者：

Kim, Yong Hyun ^{[1
]}

Yoon, Hyoung Kyu ^{[1
]}

Kim, Chi Hong ^{[1
]}

Ahn, Joong Hyun ^{[1
]}

Kwon, Soon Seog ^{[1
]}

Kim, Young Kyoon ^{[1
]}

Kim, Kwan Hyoung ^{[1
]}

Moon, Hwa Sik ^{[1
]}

Park, Sung Hak ^{[1
]}

Song, Jeong Sup ^{[1
]}

Cho, Kyung Sook ^{[2
]}

机构：

[1] Catholic Univ Korea, Coll Med, St Marys Hosp, Div Pulmonol,Dept Internal Med, Seoul, South Korea

[2] Catholic Univ Korea, Coll Med, St Marys Hosp, Inst Resp Dis, Seoul, South Korea

来源：

TUBERCULOSIS AND RESPIRATORY DISEASES | 2005年 / 58卷 / 06期

关键词：

Cigarette smoke; MUC5AC; MAPK; Signal transduction;

D O I：

10.4046/trd.2005.58.6.590

中图分类号：

R56 [呼吸系及胸部疾病];

学科分类号：

摘要：

Object : Cigarette smoking is a major cause of mucus hypersecretion, which is a pathophysiological feature of many inflammatory airway diseases. Mucins, which are an important part of the airway mucus, are synthesized from the Muc gene in airway epithelial cells. However, the signaling pathways for cigarette smoke-induced mucin synthesis are unknown. The aim of this study was to determine the signal pathway for smoking induced Muc5ac gene expression. Methods : A549 cells were cultured and transiently transfected with the Muc5ac promoter fragment. These cells were stimulated with 5% cigarette smoke extract (CSE) alone or with CSE after a pretreatment with various signal transduction pathway inhibitors (AG1478, PD98059 and SB203580). The Muc5ac promoter activity was examined using the luciferase reporter system, and the level of phosphorylated EGFR, ERK1/2, p38 MAPK and JNK were all examined using Western blot analysis. Muc5ac mRNA expression was also examined using reverse transcriptase polymerase chain reactions (RT-PCR). Results : 1. The peak level of luciferase activity of the Muc5ac promoter was observed at 5% concentration and after 3 hours of incubation with the CSE. The level of EGFR phosphorylation and the luciferase activity of the transfected cells caused by the CSE were significantly suppressed by AG1478 or PD98059 (P<0.01). 2. CSE phosphorylated ERK1/2 or p38 MAPK but not JNK. The Muc5ac mRNA expression level was increased by the CSE but that was suppressed by PD98059 or AG1478. 3. The CSE-induced phosphorylation of ERK1/2 was blocked by PD98059 and that of p38 MAPK was blocked by either PD98059 or SB203580. Either PD98059 or SB203580 suppressed the luciferase activity of the transfected cells (P<0.0001). Conclusion : The Muc5ac mRNA expression level was increased by the CSE. The increased CSE-induced transcriptional activity was mediated via EGF receptor activation, which led to ERK1/2 and p38 MAPK phosphorylation.

引用

页码：590 / 599

页数：10

共 27 条

[1] Muc-5/5ac mucin messenger RNA and protein expression is a marker of goblet cell metaplasia in murine airways [J].