摘要

There is growing evidence that increased expression of cyclooxygenase-2 (COX-2) in the lungs of patients is a key event in the pathogenesis of lung diseases. In this study, we investigated the involvement of the extracellular signal-regulated kinase (ERK), IκB kinase α/β (IKKα/β), and nuclear factor-κB (NF-κB) signaling pathways in thrombin-induced COX-2 expression in human lung fibroblasts (WI-38). Treatment of WI-38 cells with thrombin caused increased COX-2 expression in a concentration- and time-dependent manner. Treatment of WI-38 cells with PD 98059 (2-[2-amino-3-methoxyphenyl]-4H-1-benzopyran-4-one, a MEK inhibitor) inhibited thrombin-induced COX-2 expression and COX-2-luciferase activity. Stimulation of cells with thrombin caused an increase in ERK phosphorylation in a time-dependent manner. In addition, treatment of WI-38 cells with Bay 117082, an IκB phosphorylation inhibitor, and pyrrolidine dithiocarbamate (PDTC), an NF-κB inhibitor, inhibited thrombin-induced COX-2 expression. The thrombin-induced increase in COX-2-luciferase activity was also blocked by the dominant negative IκBα mutant (IκBαM). Treatment of WI-38 cells with thrombin induced IKKα/β and IκBα phosphorylation, IκBα degradation, and κB-luciferase activity. The thrombin-mediated increases in IKKα/β phosphorylation and κB-luciferase activity were inhibited by PD 98059. Taken together, these results suggest that the ERK-dependent IKKα/β/NF-κB signaling pathway plays an important role in thrombin-induced COX-2 expression in human lung fibroblasts.
原文英語
頁(從 - 到)70-75
頁數6
期刊European Journal of Pharmacology
618
發行號1-3
DOIs
出版狀態已發佈 - 九月 15 2009

指紋

Complement Factor B
Extracellular Signal-Regulated MAP Kinases
Cyclooxygenase 2
Thrombin
Fibroblasts
Lung
Luciferases
Phosphorylation
Mitogen-Activated Protein Kinase Kinases
Therapeutics
Lung Diseases
Phosphotransferases

ASJC Scopus subject areas

  • Pharmacology

引用此文

@article{330ec72540e04e4fb390c6cf68e9cdf8,
title = "Thrombin induces cyclooxygenase-2 expression via the ERK and NF-κB pathways in human lung fibroblasts",
abstract = "There is growing evidence that increased expression of cyclooxygenase-2 (COX-2) in the lungs of patients is a key event in the pathogenesis of lung diseases. In this study, we investigated the involvement of the extracellular signal-regulated kinase (ERK), IκB kinase α/β (IKKα/β), and nuclear factor-κB (NF-κB) signaling pathways in thrombin-induced COX-2 expression in human lung fibroblasts (WI-38). Treatment of WI-38 cells with thrombin caused increased COX-2 expression in a concentration- and time-dependent manner. Treatment of WI-38 cells with PD 98059 (2-[2-amino-3-methoxyphenyl]-4H-1-benzopyran-4-one, a MEK inhibitor) inhibited thrombin-induced COX-2 expression and COX-2-luciferase activity. Stimulation of cells with thrombin caused an increase in ERK phosphorylation in a time-dependent manner. In addition, treatment of WI-38 cells with Bay 117082, an IκB phosphorylation inhibitor, and pyrrolidine dithiocarbamate (PDTC), an NF-κB inhibitor, inhibited thrombin-induced COX-2 expression. The thrombin-induced increase in COX-2-luciferase activity was also blocked by the dominant negative IκBα mutant (IκBαM). Treatment of WI-38 cells with thrombin induced IKKα/β and IκBα phosphorylation, IκBα degradation, and κB-luciferase activity. The thrombin-mediated increases in IKKα/β phosphorylation and κB-luciferase activity were inhibited by PD 98059. Taken together, these results suggest that the ERK-dependent IKKα/β/NF-κB signaling pathway plays an important role in thrombin-induced COX-2 expression in human lung fibroblasts.",
keywords = "COX-2 [cyclooxygenase-2], ERK [extracellular signal-regulated kinase], IKKα/β [IκB kinase α/β], Lung fibroblast, NF-κB [nuclear factor-κB], Thrombin",
author = "Shih, {Chung Huang} and Bien, {Mauo Ying} and Chiang, {Ling Ling} and Chien-Ling Su and Lin, {Chien Huang} and Chen, {Bing Chang}",
year = "2009",
month = "9",
day = "15",
doi = "10.1016/j.ejphar.2009.07.007",
language = "English",
volume = "618",
pages = "70--75",
journal = "European Journal of Pharmacology",
issn = "0014-2999",
publisher = "Elsevier",
number = "1-3",

}

TY - JOUR

T1 - Thrombin induces cyclooxygenase-2 expression via the ERK and NF-κB pathways in human lung fibroblasts

AU - Shih, Chung Huang

AU - Bien, Mauo Ying

AU - Chiang, Ling Ling

AU - Su, Chien-Ling

AU - Lin, Chien Huang

AU - Chen, Bing Chang

PY - 2009/9/15

Y1 - 2009/9/15

N2 - There is growing evidence that increased expression of cyclooxygenase-2 (COX-2) in the lungs of patients is a key event in the pathogenesis of lung diseases. In this study, we investigated the involvement of the extracellular signal-regulated kinase (ERK), IκB kinase α/β (IKKα/β), and nuclear factor-κB (NF-κB) signaling pathways in thrombin-induced COX-2 expression in human lung fibroblasts (WI-38). Treatment of WI-38 cells with thrombin caused increased COX-2 expression in a concentration- and time-dependent manner. Treatment of WI-38 cells with PD 98059 (2-[2-amino-3-methoxyphenyl]-4H-1-benzopyran-4-one, a MEK inhibitor) inhibited thrombin-induced COX-2 expression and COX-2-luciferase activity. Stimulation of cells with thrombin caused an increase in ERK phosphorylation in a time-dependent manner. In addition, treatment of WI-38 cells with Bay 117082, an IκB phosphorylation inhibitor, and pyrrolidine dithiocarbamate (PDTC), an NF-κB inhibitor, inhibited thrombin-induced COX-2 expression. The thrombin-induced increase in COX-2-luciferase activity was also blocked by the dominant negative IκBα mutant (IκBαM). Treatment of WI-38 cells with thrombin induced IKKα/β and IκBα phosphorylation, IκBα degradation, and κB-luciferase activity. The thrombin-mediated increases in IKKα/β phosphorylation and κB-luciferase activity were inhibited by PD 98059. Taken together, these results suggest that the ERK-dependent IKKα/β/NF-κB signaling pathway plays an important role in thrombin-induced COX-2 expression in human lung fibroblasts.

AB - There is growing evidence that increased expression of cyclooxygenase-2 (COX-2) in the lungs of patients is a key event in the pathogenesis of lung diseases. In this study, we investigated the involvement of the extracellular signal-regulated kinase (ERK), IκB kinase α/β (IKKα/β), and nuclear factor-κB (NF-κB) signaling pathways in thrombin-induced COX-2 expression in human lung fibroblasts (WI-38). Treatment of WI-38 cells with thrombin caused increased COX-2 expression in a concentration- and time-dependent manner. Treatment of WI-38 cells with PD 98059 (2-[2-amino-3-methoxyphenyl]-4H-1-benzopyran-4-one, a MEK inhibitor) inhibited thrombin-induced COX-2 expression and COX-2-luciferase activity. Stimulation of cells with thrombin caused an increase in ERK phosphorylation in a time-dependent manner. In addition, treatment of WI-38 cells with Bay 117082, an IκB phosphorylation inhibitor, and pyrrolidine dithiocarbamate (PDTC), an NF-κB inhibitor, inhibited thrombin-induced COX-2 expression. The thrombin-induced increase in COX-2-luciferase activity was also blocked by the dominant negative IκBα mutant (IκBαM). Treatment of WI-38 cells with thrombin induced IKKα/β and IκBα phosphorylation, IκBα degradation, and κB-luciferase activity. The thrombin-mediated increases in IKKα/β phosphorylation and κB-luciferase activity were inhibited by PD 98059. Taken together, these results suggest that the ERK-dependent IKKα/β/NF-κB signaling pathway plays an important role in thrombin-induced COX-2 expression in human lung fibroblasts.

KW - COX-2 [cyclooxygenase-2]

KW - ERK [extracellular signal-regulated kinase]

KW - IKKα/β [IκB kinase α/β]

KW - Lung fibroblast

KW - NF-κB [nuclear factor-κB]

KW - Thrombin

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U2 - 10.1016/j.ejphar.2009.07.007

DO - 10.1016/j.ejphar.2009.07.007

M3 - Article

C2 - 19616539

AN - SCOPUS:68949180092

VL - 618

SP - 70

EP - 75

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

IS - 1-3

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