Lipoteichoic acid induces HO-1 expression via the TLR2/MyD88/c-Src/NADPH oxidase pathway and Nrf2 in human tracheal smooth muscle cells

I-Ta Lee, Shyi Wu Wang, Chiang Wen Lee, Chia Chi Chang, Chih Chung Lin, Shue Fen Luo, Chuen Mao Yang

Research output: Contribution to journalArticle

106 Citations (Scopus)

Abstract

Heme oxygenase (HO)-1 is a stress-inducible rate-limiting enzyme in heme degradation that confers cytoprotection against oxidative injury and provides a vital function in maintaining tissue homeostasis. Increasing reports have indicated that lipoteichoic acid (LTA) exerts as LPS as an immune system-stimulating agent and plays a role in the pathogenesis of severe inflammatory responses induced by Gram-positive bacterial infection. We report that LTA is an inducer of HO-1 expression mediated through the signaling pathways in human tracheal smooth muscle cells (HTSMCs). LTA-induced HO-1 protein levels, mRNA expression, and promoter activity were attenuated by transfection with dominant negative mutants of TLR2 and MyD88, by pretreatment with the inhibitors of c-Src (PP1), NADPH oxidase (diphenylene iodonium chloride (DPI) and apocynin (APO)), and reactive oxygen species (ROS) scavenger (N-acetyl-L-cysteine) or by transfection with small interfering RNAs of Src and NF-E2-related factor 2 (Nrf2). LTA-stimulated translocation of p47 phox and Nrf2 or ROS production was attenuated by transfection with dominant negative mutants of TLR2, MyD88, and c-Src and by pretreatment with DPI or APO. Furthermore, LTA-induced TLR2, MyD88, TNFR-associated factor (TRAF)6, c-Src, and p47phox complex formation was revealed by immunoprecipitation using an anti-TLR2 or anti-c-Src Ab followed by Western blot analysis against an anti-TLR2, anti-MyD88, anti-TRAF6, anti-c-Src, or anti-p47phox Ab. These results demonstrated that LTA-induced ROS generation was mediated through the TLR2/MyD88/TRAF6/c-Src/NADPH oxidase pathway, in turn initiates the activation of Nrf2, and ultimately induces HO-1 expression in HTSMCs.

Original languageEnglish
Pages (from-to)5098-5110
Number of pages13
JournalJournal of Immunology
Volume181
Issue number7
DOIs
Publication statusPublished - Oct 1 2008
Externally publishedYes

Fingerprint

NF-E2-Related Factor 2
Heme Oxygenase-1
NADPH Oxidase
Smooth Muscle Myocytes
TNF Receptor-Associated Factor 6
Transfection
Reactive Oxygen Species
Chlorides
Gram-Positive Bacterial Infections
Cytoprotection
Acetylcysteine
Heme
Immunoprecipitation
Small Interfering RNA
lipoteichoic acid
Immune System
Homeostasis
Western Blotting
Messenger RNA
Wounds and Injuries

ASJC Scopus subject areas

  • Immunology

Cite this

Lipoteichoic acid induces HO-1 expression via the TLR2/MyD88/c-Src/NADPH oxidase pathway and Nrf2 in human tracheal smooth muscle cells. / Lee, I-Ta; Wang, Shyi Wu; Lee, Chiang Wen; Chang, Chia Chi; Lin, Chih Chung; Luo, Shue Fen; Yang, Chuen Mao.

In: Journal of Immunology, Vol. 181, No. 7, 01.10.2008, p. 5098-5110.

Research output: Contribution to journalArticle

Lee, I-Ta ; Wang, Shyi Wu ; Lee, Chiang Wen ; Chang, Chia Chi ; Lin, Chih Chung ; Luo, Shue Fen ; Yang, Chuen Mao. / Lipoteichoic acid induces HO-1 expression via the TLR2/MyD88/c-Src/NADPH oxidase pathway and Nrf2 in human tracheal smooth muscle cells. In: Journal of Immunology. 2008 ; Vol. 181, No. 7. pp. 5098-5110.
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abstract = "Heme oxygenase (HO)-1 is a stress-inducible rate-limiting enzyme in heme degradation that confers cytoprotection against oxidative injury and provides a vital function in maintaining tissue homeostasis. Increasing reports have indicated that lipoteichoic acid (LTA) exerts as LPS as an immune system-stimulating agent and plays a role in the pathogenesis of severe inflammatory responses induced by Gram-positive bacterial infection. We report that LTA is an inducer of HO-1 expression mediated through the signaling pathways in human tracheal smooth muscle cells (HTSMCs). LTA-induced HO-1 protein levels, mRNA expression, and promoter activity were attenuated by transfection with dominant negative mutants of TLR2 and MyD88, by pretreatment with the inhibitors of c-Src (PP1), NADPH oxidase (diphenylene iodonium chloride (DPI) and apocynin (APO)), and reactive oxygen species (ROS) scavenger (N-acetyl-L-cysteine) or by transfection with small interfering RNAs of Src and NF-E2-related factor 2 (Nrf2). LTA-stimulated translocation of p47 phox and Nrf2 or ROS production was attenuated by transfection with dominant negative mutants of TLR2, MyD88, and c-Src and by pretreatment with DPI or APO. Furthermore, LTA-induced TLR2, MyD88, TNFR-associated factor (TRAF)6, c-Src, and p47phox complex formation was revealed by immunoprecipitation using an anti-TLR2 or anti-c-Src Ab followed by Western blot analysis against an anti-TLR2, anti-MyD88, anti-TRAF6, anti-c-Src, or anti-p47phox Ab. These results demonstrated that LTA-induced ROS generation was mediated through the TLR2/MyD88/TRAF6/c-Src/NADPH oxidase pathway, in turn initiates the activation of Nrf2, and ultimately induces HO-1 expression in HTSMCs.",
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AU - Wang, Shyi Wu

AU - Lee, Chiang Wen

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AU - Lin, Chih Chung

AU - Luo, Shue Fen

AU - Yang, Chuen Mao

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