Resveratrol inhibits Staphylococcus aureus-induced TLR2/MyD88/NF-κB-dependent VCAM-1 expression in human lung epithelial cells

2014 ◽  
Vol 127 (6) ◽  
pp. 375-390 ◽  
Author(s):  
I-Ta Lee ◽  
Chih-Chung Lin ◽  
Chih-Kai Hsu ◽  
Ming-Yen Wu ◽  
Rou-Ling Cho ◽  
...  

In the present study, we found that S. aureus induced VCAM-1 expression in human pulmonary alveolar epithelial cells via a TLR2/MyD88/NF-κB-dependent pathway, which was inhibited by treatment with the polyphenolic compound resveratrol.

Data in Brief ◽  
2016 ◽  
Vol 7 ◽  
pp. 1031-1037 ◽  
Author(s):  
Kristin Surmann ◽  
Marjolaine Simon ◽  
Petra Hildebrandt ◽  
Henrike Pförtner ◽  
Stephan Michalik ◽  
...  

2014 ◽  
Vol 306 (7) ◽  
pp. C648-C658 ◽  
Author(s):  
Hanying Zhang ◽  
Miyako Okamoto ◽  
Evgeniy Panzhinskiy ◽  
W. Michael Zawada ◽  
Mita Das

Epithelial cells are key players in the pathobiology of numerous hypoxia-induced lung diseases. The mechanisms mediating such hypoxic responses of epithelial cells are not well characterized. Earlier studies reported that hypoxia stimulates protein kinase C (PKC)δ activation in renal cancer cells and an increase in expression of a heparin-binding growth factor, midkine (MK), in lung alveolar epithelial cells. We reasoned that hypoxia might regulate MK levels via a PKCδ-dependent pathway and hypothesized that PKCδ-driven MK expression is required for hypoxia-induced lung epithelial cell proliferation and differentiation. Replication of human lung epithelial cells (A549) was significantly increased by chronic hypoxia (1% O2) and was dependent on expression of PKCδ. Hypoxia-induced proliferation of epithelial cells was accompanied by translocation of PKCδ from Golgi into the nuclei. Marked attenuation in MK protein levels by rottlerin, a pharmacological antagonist of PKC, and by small interfering RNA-targeting PKCδ, revealed that PKCδ is required for MK expression in both normoxic and hypoxic lung epithelial cells. Sequestering MK secreted into the culture media with a neutralizing antibody reduced hypoxia-induced proliferation demonstrating that an increase in MK release from cells is linked with epithelial cell division under hypoxia. In addition, recombinant MK accelerated transition of hypoxic epithelial cells to cells of mesenchymal phenotype characterized by elongated morphology and increased expression of mesenchymal markers, α-smooth muscle actin, and vimentin. We conclude that PKCδ/MK axis mediates hypoxic proliferation and differentiation of lung epithelial cells. Manipulation of PKCδ and MK activity in epithelial cells might be beneficial for the treatment of hypoxia-mediated lung diseases.


2018 ◽  
Vol 19 (10) ◽  
pp. 3058 ◽  
Author(s):  
I-Ta Lee ◽  
Chih-Chung Lin ◽  
Chien-Chung Yang ◽  
Li-Der Hsiao ◽  
Ming-Yen Wu ◽  
...  

Staphylococcus aureus (S. aureus) is a very common Gram-positive bacterium. It is widely distributed in air, soil, and water. S. aureus often causes septicemia and pneumonia in patients. In addition, it is considered to play a key role in mediating cell adhesion molecules upregulation. Resveratrol is a natural antioxidant with diverse biological effects, including the modulation of immune function, anti-inflammation, and cancer chemoprevention. In this study, we proved that S. aureus-upregulated vascular cell adhesion molecule-1 (VCAM-1) expression in human lung epithelial cells (HPAEpiCs) was inhibited by resveratrol. We also observed that resveratrol downregulated S. aureus-enhanced leukocyte count in bronchoalveolar lavage (BAL) fluid in mice. In HPAEpiCs, S. aureus stimulated c-Src, PDGFR, p38 MAPK, or JNK1/2 phosphorylation, which was inhibited by resveratrol. S. aureus induced the adhesion of THP-1 cells (a human monocytic cell line) to HPAEpiCs, which was also reduced by resveratrol. Finally, we found that S. aureus induced c-Src/PDGFR/p38 MAPK and JNK1/2-dependent c-Jun and ATF2 activation and in vivo binding of c-Jun and ATF2 to the VCAM-1 promoter, which were inhibited by resveratrol. Thus, resveratrol functions as a suppressor of S. aureus-induced inflammatory signaling, not only by inhibiting VCAM-1 expression but also by diminishing c-Src, PDGFR, JNK1/2, p38 MAPK, and AP-1 activation in HPAEpiCs.


Pneumologie ◽  
2010 ◽  
Vol 64 (S 03) ◽  
Author(s):  
B Schmeck ◽  
B Dolniak ◽  
I Pollock ◽  
C Schulz ◽  
W Bertrams ◽  
...  

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