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Quercetin inhibits IL-1 beta-induced ICAM-1 expression in pulmonary epithelial cell line A549 through the MAPK pathways

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Abstract

Quercetin is a herbal flavonoid derived from various foods of plant origin and widely used as a major constituent of nutritional supplements. Quercetin has been shown to have anti-inflammatory properties and can play a role in anti-inflammatory procedure. Intercellular adhesion molecule-1 (ICAM-1) is one of the important pro-inflammatory factors, especially in early phage of inflammation. However, the mechanisms regulating ICAM-1 expression by quercetin in human A549 cells were still unclear. In this study, the inhibitory effect of quercetin on ICAM-1 expression by interleukin-1 beta (IL-1 beta)-stimulated A549 cells was investigated, and the roles of mitogen-activated protein kinases (MAPK) pathways were explored. Quercetin attenuated IL-1 beta-induced expression of ICAM-1 mRNA and protein in a dose-dependent manner. The experiment suggested that quercetin actively inhibited inhibitory protein of nuclear factor-kappa B (I kappa B) degradation, and nuclear factor-kappa B (NF-kappa B) activity. The c-fos and c-jun, components of activator protein-1 (AP-1), were mediated by MAPK pathways. ERK and p38 were involved in the c-fos mRNA expression, and JNK was involved in the c-jun mRNA expression. The inhibitory effect of quercetin on ICAM-1 expression was mediated by the sequential attenuation of the c-fos and c-jun mRNA expressions. These inhibitory effects were partially inhibited by SB203580, a specific inhibitor of p38 MAPK, but not by PD98059, a specific inhibitors of extracellular signal-regulated kinase (ERK), and SP600125, a specific inhibitor of c-Jun-N-terminal kinase (JNK). Taken together, these results suggest that quercetin negatively modulating ICAM-1 partly dependent on MAPK pathways.

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Abbreviations

ICAM-1:

Intercellular adhesion molecule-1

ERK:

Extracellular signal-regulated kinase

JNK:

c-jun NH2-terminal kinase

NF-kappa B:

Nuclear factor-kappa B

I kappa B:

Inhibitory protein of nuclear factor-kappa B

IL-1 beta:

Interleukin-1 beta

MAPK:

Mitogen activated protein kinase

AP-1:

Activator protein-1

TNF-alpha:

Tumor necrosis factor-alpha

MTT:

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide

DMSO:

Dimethylsulfoxide

RT-PCR:

Reverse transcription-polymerase chain reaction

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Acknowledgments

This study was supported by Grants #30425007, 30370627, 30670921 from National Natural Science Foundation of China and 00–722, 06–834 from China Medical Board of New York to Dr. F.Q. Wen.

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Authors and Affiliations

  1. Department of Lab Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China

    Binwu Ying, Xingbo Song, Hong Fan & Xiaojun Lu

  2. Division of Pulmonary Disease, State Key Laboratory of Biotherapy and Department of Respiratory Medicine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China

    Ting Yang, Xiaobo Hu, Lijuan Chen, Deyun Cheng, Tao Wang, Daishun Liu, Dan Xu, Yuquan Wei & Fuqiang Wen

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  1. Binwu Ying
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  13. Fuqiang Wen
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Correspondence to Fuqiang Wen.

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Binwu Ying and Ting Yang have contributed equally to this work.

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Ying, B., Yang, T., Song, X. et al. Quercetin inhibits IL-1 beta-induced ICAM-1 expression in pulmonary epithelial cell line A549 through the MAPK pathways. Mol Biol Rep 36, 1825–1832 (2009). https://doi.org/10.1007/s11033-008-9386-1

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  • DOI: https://doi.org/10.1007/s11033-008-9386-1

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