Abstract

A previous report showed that transforming growth factor-β1 (TGF-β1) can induce heme oxygenase-1 (HO-1) expression, attenuate cellular injury, and maintain tissue homeostasis. In this study, we investigated the involvement of phosphoinositide-3-OH-kinase (PI3K)/Akt and the nuclear factor-κB (NF-κB) signaling pathway in TGF-β1-induced HO-1 expression in human lung epithelial cells (A549). Treatment of A549 cells with TGF-β1 caused HO-1 to be expressed in a concentration- and time-dependent manner. Treatment of A549 cells with LY 294002 (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one, a PI3K inhibitor), an Akt inhibitor, and the dominant negative mutant of Akt (Akt DN) inhibited TGF-β1-induced HO-1 expression and HO-1-luciferase activity. Stimulation of cells with TGF-β1 caused an increase in Akt phosphorylation in a time-dependent manner, which was inhibited by wortmannin and LY 294002 (PI3K inhibitors). In addition, treatment of A549 cells with Bay 117082 ((E)-3-[4-methylphenylsulfonyl]-2-propenenitrile, an IκB phosphorylation inhibitor), pyrrolidine dithiocarbamate (PDTC, an NF-κB inhibitor), and the dominant negative mutant of IκBα (IκBαM) inhibited TGF-β1-induced HO-1 expression and HO-1-luciferase activity. Treatment of A549 cells with TGF-β1-induced IκB kinase α/β (IKKα/β) phosphorylation, IκBα phosphorylation, IκBα degradation, p65 Ser536 phosphorylation, and κB-luciferase activity. The TGF-β1-mediated increases in IKKα/β phosphorylation, p65 Ser536 phosphorylation, and κB-luciferase activity were inhibited by LY 294002, an Akt inhibitor, and Akt DN. Taken together, these results suggest that the PI3K/Akt dependent IKKα/β/NF-κB signaling pathway plays an important role in TGF-β1-induced HO-1 expression in A549 cells.

Original languageEnglish
Pages (from-to)101-109
Number of pages9
JournalEuropean Journal of Pharmacology
Volume560
Issue number2-3
DOIs
Publication statusPublished - Apr 10 2007

Fingerprint

Heme Oxygenase-1
Transforming Growth Factors
Phosphatidylinositols
Phosphotransferases
Epithelial Cells
Lung
Phosphorylation
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Luciferases
hydroxide ion
Homeostasis
A549 Cells
Wounds and Injuries

Keywords

  • Akt
  • HO-1 [Heme oxygenase-1]
  • Human lung epithelial cell
  • NF-κB [Nuclear factor-κB]
  • PI3K [Phosphoinositide-3-OH-kinase]
  • TGF-β1 [Transforming growth factor-β1]

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

@article{634af00f5ba3401c9742727848855e66,
title = "Transforming growth factor-β1 stimulates heme oxygenase-1 expression via the PI3K/Akt and NF-κB pathways in human lung epithelial cells",
abstract = "A previous report showed that transforming growth factor-β1 (TGF-β1) can induce heme oxygenase-1 (HO-1) expression, attenuate cellular injury, and maintain tissue homeostasis. In this study, we investigated the involvement of phosphoinositide-3-OH-kinase (PI3K)/Akt and the nuclear factor-κB (NF-κB) signaling pathway in TGF-β1-induced HO-1 expression in human lung epithelial cells (A549). Treatment of A549 cells with TGF-β1 caused HO-1 to be expressed in a concentration- and time-dependent manner. Treatment of A549 cells with LY 294002 (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one, a PI3K inhibitor), an Akt inhibitor, and the dominant negative mutant of Akt (Akt DN) inhibited TGF-β1-induced HO-1 expression and HO-1-luciferase activity. Stimulation of cells with TGF-β1 caused an increase in Akt phosphorylation in a time-dependent manner, which was inhibited by wortmannin and LY 294002 (PI3K inhibitors). In addition, treatment of A549 cells with Bay 117082 ((E)-3-[4-methylphenylsulfonyl]-2-propenenitrile, an IκB phosphorylation inhibitor), pyrrolidine dithiocarbamate (PDTC, an NF-κB inhibitor), and the dominant negative mutant of IκBα (IκBαM) inhibited TGF-β1-induced HO-1 expression and HO-1-luciferase activity. Treatment of A549 cells with TGF-β1-induced IκB kinase α/β (IKKα/β) phosphorylation, IκBα phosphorylation, IκBα degradation, p65 Ser536 phosphorylation, and κB-luciferase activity. The TGF-β1-mediated increases in IKKα/β phosphorylation, p65 Ser536 phosphorylation, and κB-luciferase activity were inhibited by LY 294002, an Akt inhibitor, and Akt DN. Taken together, these results suggest that the PI3K/Akt dependent IKKα/β/NF-κB signaling pathway plays an important role in TGF-β1-induced HO-1 expression in A549 cells.",
keywords = "Akt, HO-1 [Heme oxygenase-1], Human lung epithelial cell, NF-κB [Nuclear factor-κB], PI3K [Phosphoinositide-3-OH-kinase], TGF-β1 [Transforming growth factor-β1]",
author = "Lin, {Chen Chun} and Chiang, {Ling Ling} and Lin, {Chien Huang} and Shih, {Chung Hung} and Liao, {Yi Ting} and Hsu, {Ming Jen} and Chen, {Bing Chang}",
year = "2007",
month = "4",
day = "10",
doi = "10.1016/j.ejphar.2007.01.025",
language = "English",
volume = "560",
pages = "101--109",
journal = "European Journal of Pharmacology",
issn = "0014-2999",
publisher = "Elsevier",
number = "2-3",

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TY - JOUR

T1 - Transforming growth factor-β1 stimulates heme oxygenase-1 expression via the PI3K/Akt and NF-κB pathways in human lung epithelial cells

AU - Lin, Chen Chun

AU - Chiang, Ling Ling

AU - Lin, Chien Huang

AU - Shih, Chung Hung

AU - Liao, Yi Ting

AU - Hsu, Ming Jen

AU - Chen, Bing Chang

PY - 2007/4/10

Y1 - 2007/4/10

N2 - A previous report showed that transforming growth factor-β1 (TGF-β1) can induce heme oxygenase-1 (HO-1) expression, attenuate cellular injury, and maintain tissue homeostasis. In this study, we investigated the involvement of phosphoinositide-3-OH-kinase (PI3K)/Akt and the nuclear factor-κB (NF-κB) signaling pathway in TGF-β1-induced HO-1 expression in human lung epithelial cells (A549). Treatment of A549 cells with TGF-β1 caused HO-1 to be expressed in a concentration- and time-dependent manner. Treatment of A549 cells with LY 294002 (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one, a PI3K inhibitor), an Akt inhibitor, and the dominant negative mutant of Akt (Akt DN) inhibited TGF-β1-induced HO-1 expression and HO-1-luciferase activity. Stimulation of cells with TGF-β1 caused an increase in Akt phosphorylation in a time-dependent manner, which was inhibited by wortmannin and LY 294002 (PI3K inhibitors). In addition, treatment of A549 cells with Bay 117082 ((E)-3-[4-methylphenylsulfonyl]-2-propenenitrile, an IκB phosphorylation inhibitor), pyrrolidine dithiocarbamate (PDTC, an NF-κB inhibitor), and the dominant negative mutant of IκBα (IκBαM) inhibited TGF-β1-induced HO-1 expression and HO-1-luciferase activity. Treatment of A549 cells with TGF-β1-induced IκB kinase α/β (IKKα/β) phosphorylation, IκBα phosphorylation, IκBα degradation, p65 Ser536 phosphorylation, and κB-luciferase activity. The TGF-β1-mediated increases in IKKα/β phosphorylation, p65 Ser536 phosphorylation, and κB-luciferase activity were inhibited by LY 294002, an Akt inhibitor, and Akt DN. Taken together, these results suggest that the PI3K/Akt dependent IKKα/β/NF-κB signaling pathway plays an important role in TGF-β1-induced HO-1 expression in A549 cells.

AB - A previous report showed that transforming growth factor-β1 (TGF-β1) can induce heme oxygenase-1 (HO-1) expression, attenuate cellular injury, and maintain tissue homeostasis. In this study, we investigated the involvement of phosphoinositide-3-OH-kinase (PI3K)/Akt and the nuclear factor-κB (NF-κB) signaling pathway in TGF-β1-induced HO-1 expression in human lung epithelial cells (A549). Treatment of A549 cells with TGF-β1 caused HO-1 to be expressed in a concentration- and time-dependent manner. Treatment of A549 cells with LY 294002 (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one, a PI3K inhibitor), an Akt inhibitor, and the dominant negative mutant of Akt (Akt DN) inhibited TGF-β1-induced HO-1 expression and HO-1-luciferase activity. Stimulation of cells with TGF-β1 caused an increase in Akt phosphorylation in a time-dependent manner, which was inhibited by wortmannin and LY 294002 (PI3K inhibitors). In addition, treatment of A549 cells with Bay 117082 ((E)-3-[4-methylphenylsulfonyl]-2-propenenitrile, an IκB phosphorylation inhibitor), pyrrolidine dithiocarbamate (PDTC, an NF-κB inhibitor), and the dominant negative mutant of IκBα (IκBαM) inhibited TGF-β1-induced HO-1 expression and HO-1-luciferase activity. Treatment of A549 cells with TGF-β1-induced IκB kinase α/β (IKKα/β) phosphorylation, IκBα phosphorylation, IκBα degradation, p65 Ser536 phosphorylation, and κB-luciferase activity. The TGF-β1-mediated increases in IKKα/β phosphorylation, p65 Ser536 phosphorylation, and κB-luciferase activity were inhibited by LY 294002, an Akt inhibitor, and Akt DN. Taken together, these results suggest that the PI3K/Akt dependent IKKα/β/NF-κB signaling pathway plays an important role in TGF-β1-induced HO-1 expression in A549 cells.

KW - Akt

KW - HO-1 [Heme oxygenase-1]

KW - Human lung epithelial cell

KW - NF-κB [Nuclear factor-κB]

KW - PI3K [Phosphoinositide-3-OH-kinase]

KW - TGF-β1 [Transforming growth factor-β1]

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U2 - 10.1016/j.ejphar.2007.01.025

DO - 10.1016/j.ejphar.2007.01.025

M3 - Article

C2 - 17307160

AN - SCOPUS:33847381862

VL - 560

SP - 101

EP - 109

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

IS - 2-3

ER -