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A Mouse Model to Assess Innate Immune Response to Staphylococcus aureus Infection
Published on: February 28, 2019
Resveratrol inhibits Staphylococcus aureus-induced TLR2/MyD88/NF-κB-dependent VCAM-1 expression in human lung
I-Ta Lee1, Chih-Chung Lin2, Chih-Kai Hsu1
1*Department of Physiology and Pharmacology and Health Aging Research Center, College of Medicine, Chang Gung University, Kwei-San, Tao-Yuan, Taiwan.
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.
Insights
Resveratrol, found in red fruits, reduces inflammation caused by Staphylococcus aureus lung infections. This compound inhibits key signaling pathways, offering potential therapeutic benefits for S. aureus-induced lung diseases.
Area of Science:
- Immunology
- Pharmacology
- Molecular Biology
Background:
- Staphylococcus aureus is a common cause of intensive-care unit infections like pneumonia and septicaemia.
- S. aureus plays a significant role in inducing cell adhesion molecules, contributing to inflammatory responses.
- Resveratrol, a natural compound, has potential anti-inflammatory properties relevant to lung diseases.
Purpose of the Study:
- To investigate the inhibitory effects of resveratrol on Staphylococcus aureus-mediated inflammatory responses.
- To elucidate the molecular mechanisms by which resveratrol suppresses S. aureus-induced inflammation in lung epithelial cells and in vivo.
Main Methods:
- In vitro studies using human lung epithelial cells (HPAEpiCs) and in vivo studies using mouse models.
- Assessed resveratrol's impact on S. aureus-induced VCAM-1 expression, pulmonary haematoma, and leukocyte counts.
- Investigated the modulation of signaling pathways including TLR2, MyD88, PI3K, Akt, JNK1/2, p42/p44 MAPK, NF-κB, and p300.
Main Results:
- Resveratrol significantly reduced S. aureus-induced VCAM-1 expression in HPAEpiCs and mouse lungs.
- In vivo, resveratrol inhibited S. aureus-induced pulmonary damage and reduced leukocyte infiltration in bronchoalveolar lavage fluid.
- Resveratrol attenuated the formation of TLR2-MyD88-PI3K complexes and inhibited the phosphorylation and activation of downstream signaling molecules like Akt, JNK1/2, p42/p44 MAPK, p300, and NF-κB.
Conclusions:
- Resveratrol acts as a suppressor of S. aureus-induced inflammatory signaling in lung epithelial cells.
- The compound inhibits VCAM-1 expression and modulates critical inflammatory pathways, including TLR2-MyD88-PI3K signaling and NF-κB activation.
- Resveratrol demonstrates therapeutic potential for managing S. aureus-related lung inflammation and diseases.
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