Staphylococcus aureus is the most commonly found Gram-positive bacterium in patients admitted to intensive-care units, causing septicaemia or pneumonia. S. aureus is considered to play an important role in the induction of cell adhesion molecules. Resveratrol, a compound found in the skins of red fruits, may inhibit the inflammatory signalling pathways involved in lung diseases. In the present paper, we have shown that resveratrol reduced S. aureus-mediated VCAM-1 (vascular cell adhesion molecule-1) expression in HPAEpiCs (human lung epithelial cells) and lungs of mice. In an in vivo study, we have shown that resveratrol inhibited S. aureus-induced pulmonary haematoma and leucocyte count in BAL (bronchoalveolar lavage) fluid in mice. In an in vitro study, we observed that resveratrol attenuated S. aureus-induced TLR2 (Toll-like receptor 2), MyD88 (myeloid differentiation factor 88) and PI3K (phosphoinositide 3-kinase) complex formation. S. aureus stimulated Akt, JNK1/2 (c-Jun N-terminal kinase 1/2) and p42/p44 MAPK (mitogen-activated protein kinase) phosphorylation, which were inhibited by resveratrol. In addition, S. aureus induced IκB (inhibitor of nuclear factor κB) α and NF-κB (nuclear factor κB) p65 phosphorylation and NF-κB p65 translocation, which were reduced by resveratrol. Finally, we found that S. aureus induced NF-κB and p300 complex formation and p300 phosphorylation, which were inhibited by resveratrol. Thus resveratrol functions as a suppressor of S. aureus-induced inflammatory signalling not only by inhibiting VCAM-1 expression, but also by reducing TLR2–MyD88–PI3K complex formation and Akt, JNK1/2, p42/p44 MAPK, p300 and NF-κB activation in HPAEpiCs.
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May 29 2014
Resveratrol inhibits Staphylococcus aureus-induced TLR2/MyD88/NF-κB-dependent VCAM-1 expression in human lung epithelial cells
I-Ta Lee;
I-Ta Lee
1
*Department of Physiology and Pharmacology and Health Aging Research Center, College of Medicine, Chang Gung University, Kwei-San, Tao-Yuan, Taiwan
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Chih-Chung Lin;
Chih-Chung Lin
1
†Department of Anesthetics, Chang Gung Memorial Hospital at Linkuo and Chang Gung University, Kwei-San, Tao-Yuan, Taiwan
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Chih-Kai Hsu;
Chih-Kai Hsu
*Department of Physiology and Pharmacology and Health Aging Research Center, College of Medicine, Chang Gung University, Kwei-San, Tao-Yuan, Taiwan
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Ming-Yen Wu;
Ming-Yen Wu
*Department of Physiology and Pharmacology and Health Aging Research Center, College of Medicine, Chang Gung University, Kwei-San, Tao-Yuan, Taiwan
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Rou-Ling Cho;
Rou-Ling Cho
*Department of Physiology and Pharmacology and Health Aging Research Center, College of Medicine, Chang Gung University, Kwei-San, Tao-Yuan, Taiwan
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Chuen-Mao Yang
*Department of Physiology and Pharmacology and Health Aging Research Center, College of Medicine, Chang Gung University, Kwei-San, Tao-Yuan, Taiwan
Correspondence: Dr Chuen-Mao Yang (email [email protected]).
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Publisher: Portland Press Ltd
Received:
December 13 2013
Revision Received:
February 14 2014
Accepted:
March 12 2014
Accepted Manuscript online:
March 12 2014
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2014 Biochemical Society
2014
Clin Sci (Lond) (2014) 127 (6): 375–390.
Article history
Received:
December 13 2013
Revision Received:
February 14 2014
Accepted:
March 12 2014
Accepted Manuscript online:
March 12 2014
Citation
I-Ta Lee, Chih-Chung Lin, Chih-Kai Hsu, Ming-Yen Wu, Rou-Ling Cho, Chuen-Mao Yang; Resveratrol inhibits Staphylococcus aureus-induced TLR2/MyD88/NF-κB-dependent VCAM-1 expression in human lung epithelial cells. Clin Sci (Lond) 1 September 2014; 127 (6): 375–390. doi: https://doi.org/10.1042/CS20130816
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