Infection with Staphylococcus aureus elicits COX-2/PGE 2 /IL-6/MMP-9-dependent aorta inflammation via the inhibition of intracellular ROS production

Ming Horng Tsai, Cheng Hsun Wu, Wei Ning Lin, Ching Yi Cheng, Chu Chun Chuang, Kuo Ting Chang, Rong San Jiang, Jen Fu Hsu, I. Ta Lee

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Staphylococcus aureus (S. aureus) can lead to many life-threatening diseases. It has the ability to invade normal endovascular tissue. The molecular mechanisms and pathological changes of endothelial cells after S. aureus infection are of interest, but the basic understanding of how S. aureus destroys this barrier is not clear. Here, we showed that S. aureus enhanced COX-2 expression and prostaglandin E 2 (PGE 2 ) secretion in human aortic endothelial cells (HAECs). In addition, S. aureus induced PGE 2 /interleukin-6 (IL-6)/matrix metallopeptidase-9 (MMP-9)-dependent cell migration. S. aureus-induced COX-2, IL-6, and MMP-9 levels were inhibited by transfection with siRNA of Toll-like receptor 2 (TLR2), p38, p42, p44, p50, or p65. S. aureus also induced p38 MAPK, ATF2, ERK1/2, and NF-κB p65 activation. Interestingly, we proved that S. aureus decreased intracellular generation of reactive oxygen species (ROS), which suggests that the inhibition of ROS production promoted inflammatory responses. Finally, we showed that S. aureus enhanced a variety of biomarkers of inflammation in cardiovascular diseases. However, the free radical scavenger (MCI-186) or antioxidant (N-acetyl-L-cysteine, NAC) markedly enhanced S. aureus-induced COX-2 mRNA levels in the aorta tissues. Taken together, these findings established that S. aureus promoted aorta inflammation via activation of p38 MAPK, ERK1/2, and NF-κB and inhibition of ROS generation.

Original languageEnglish
Pages (from-to)889-900
Number of pages12
JournalBiomedicine and Pharmacotherapy
Volume107
DOIs
Publication statusPublished - Nov 1 2018
Externally publishedYes

Fingerprint

Metalloproteases
Prostaglandins E
Aorta
Staphylococcus aureus
Interleukin-6
Reactive Oxygen Species
Inflammation
Infection
p38 Mitogen-Activated Protein Kinases
Endothelial Cells
Toll-Like Receptor 2
Free Radical Scavengers
Acetylcysteine
Small Interfering RNA
Cell Movement
Transfection
Cardiovascular Diseases
Antioxidants
Biomarkers
Messenger RNA

Keywords

  • Aorta inflammation
  • Cyclooxygenase-2
  • Interleukin-6
  • Matrix metallopeptidase-9
  • Staphylococcus aureus

ASJC Scopus subject areas

  • Pharmacology

Cite this

Infection with Staphylococcus aureus elicits COX-2/PGE 2 /IL-6/MMP-9-dependent aorta inflammation via the inhibition of intracellular ROS production. / Tsai, Ming Horng; Wu, Cheng Hsun; Lin, Wei Ning; Cheng, Ching Yi; Chuang, Chu Chun; Chang, Kuo Ting; Jiang, Rong San; Hsu, Jen Fu; Lee, I. Ta.

In: Biomedicine and Pharmacotherapy, Vol. 107, 01.11.2018, p. 889-900.

Research output: Contribution to journalArticle

Tsai, Ming Horng ; Wu, Cheng Hsun ; Lin, Wei Ning ; Cheng, Ching Yi ; Chuang, Chu Chun ; Chang, Kuo Ting ; Jiang, Rong San ; Hsu, Jen Fu ; Lee, I. Ta. / Infection with Staphylococcus aureus elicits COX-2/PGE 2 /IL-6/MMP-9-dependent aorta inflammation via the inhibition of intracellular ROS production. In: Biomedicine and Pharmacotherapy. 2018 ; Vol. 107. pp. 889-900.
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AU - Tsai, Ming Horng

AU - Wu, Cheng Hsun

AU - Lin, Wei Ning

AU - Cheng, Ching Yi

AU - Chuang, Chu Chun

AU - Chang, Kuo Ting

AU - Jiang, Rong San

AU - Hsu, Jen Fu

AU - Lee, I. Ta

PY - 2018/11/1

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AB - Staphylococcus aureus (S. aureus) can lead to many life-threatening diseases. It has the ability to invade normal endovascular tissue. The molecular mechanisms and pathological changes of endothelial cells after S. aureus infection are of interest, but the basic understanding of how S. aureus destroys this barrier is not clear. Here, we showed that S. aureus enhanced COX-2 expression and prostaglandin E 2 (PGE 2 ) secretion in human aortic endothelial cells (HAECs). In addition, S. aureus induced PGE 2 /interleukin-6 (IL-6)/matrix metallopeptidase-9 (MMP-9)-dependent cell migration. S. aureus-induced COX-2, IL-6, and MMP-9 levels were inhibited by transfection with siRNA of Toll-like receptor 2 (TLR2), p38, p42, p44, p50, or p65. S. aureus also induced p38 MAPK, ATF2, ERK1/2, and NF-κB p65 activation. Interestingly, we proved that S. aureus decreased intracellular generation of reactive oxygen species (ROS), which suggests that the inhibition of ROS production promoted inflammatory responses. Finally, we showed that S. aureus enhanced a variety of biomarkers of inflammation in cardiovascular diseases. However, the free radical scavenger (MCI-186) or antioxidant (N-acetyl-L-cysteine, NAC) markedly enhanced S. aureus-induced COX-2 mRNA levels in the aorta tissues. Taken together, these findings established that S. aureus promoted aorta inflammation via activation of p38 MAPK, ERK1/2, and NF-κB and inhibition of ROS generation.

KW - Aorta inflammation

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KW - Matrix metallopeptidase-9

KW - Staphylococcus aureus

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