title: Resveratrol inhibits Staphylococcus aureus-induced TLR2/MyD88/NF-κB-dependent VCAM-1 expression in human lung epithelial cells.
abstract: 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.
authors.affiliation: *Department of Physiology and Pharmacology and Health Aging Research Center, College of Medicine, Chang Gung University, Kwei-San, Tao-Yuan, Taiwan.
authors.forename: I-Ta
authors.initials: IT
authors.lastname: Lee
authors.affiliation: †Department of Anesthetics, Chang Gung Memorial Hospital at Linkuo and Chang Gung University, Kwei-San, Tao-Yuan, Taiwan.
authors.forename: Chih-Chung
authors.initials: CC
authors.lastname: Lin
authors.affiliation: *Department of Physiology and Pharmacology and Health Aging Research Center, College of Medicine, Chang Gung University, Kwei-San, Tao-Yuan, Taiwan.
authors.forename: Chih-Kai
authors.initials: CK
authors.lastname: Hsu
authors.affiliation: *Department of Physiology and Pharmacology and Health Aging Research Center, College of Medicine, Chang Gung University, Kwei-San, Tao-Yuan, Taiwan.
authors.forename: Ming-Yen
authors.initials: MY
authors.lastname: Wu
authors.affiliation: *Department of Physiology and Pharmacology and Health Aging Research Center, College of Medicine, Chang Gung University, Kwei-San, Tao-Yuan, Taiwan.
authors.forename: Rou-Ling
authors.initials: RL
authors.lastname: Cho
authors.affiliation: *Department of Physiology and Pharmacology and Health Aging Research Center, College of Medicine, Chang Gung University, Kwei-San, Tao-Yuan, Taiwan.
authors.forename: Chuen-Mao
authors.initials: CM
authors.lastname: Yang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000302:isolation & purification; D013267:Stilbenes / Q000494:pharmacology*; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
chemical_list: D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D013267:Stilbenes; D051195:Toll-Like Receptor 2; D019010:Vascular Cell Adhesion Molecule-1; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; D000077185:Resveratrol