TY - JOUR
T1 - Infection with Staphylococcus aureus elicits COX-2/PGE
2
/IL-6/MMP-9-dependent aorta inflammation via the inhibition of intracellular ROS production
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
N1 - Funding Information:
This work was supported by the Chang Gung Medical Research Foundation , grant number CMRPGMF0022 and CMRPGMF0023 ; the China Medical University , grant number CMU106-S-14 and CMU105-S-46 .
Publisher Copyright:
© 2018
PY - 2018/11/1
Y1 - 2018/11/1
N2 - 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.
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
KW - Cyclooxygenase-2
KW - Interleukin-6
KW - Matrix metallopeptidase-9
KW - Staphylococcus aureus
UR - http://www.scopus.com/inward/record.url?scp=85051774282&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85051774282&partnerID=8YFLogxK
U2 - 10.1016/j.biopha.2018.08.096
DO - 10.1016/j.biopha.2018.08.096
M3 - Article
C2 - 30257401
AN - SCOPUS:85051774282
SN - 0753-3322
VL - 107
SP - 889
EP - 900
JO - Biomedicine and Pharmacotherapy
JF - Biomedicine and Pharmacotherapy
ER -
