Quercetin inhibits IL-1 beta-induced ICAM-1 expression in pulmonary epithelial cell line A549 through the MAPK pathways.
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.
Ying
Binwu
B
Department of Lab Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
Yang
Ting
T
Song
Xingbo
X
Hu
Xiaobo
X
Fan
Hong
H
Lu
Xiaojun
X
Chen
Lijuan
L
Cheng
Deyun
D
Wang
Tao
T
Liu
Daishun
D
Xu
Dan
D
Wei
Yuquan
Y
Wen
Fuqiang
F
D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000187:drug effects* / Q000201:enzymology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D053583:Interleukin-1beta / Q000494:pharmacology*; D008168:Lung / Q000166:cytology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D016328:NF-kappa B / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D011794:Quercetin / Q000737:chemistry / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D020672:I-kappa B Proteins; D053583:Interleukin-1beta; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D011794:Quercetin; D020928:Mitogen-Activated Protein Kinases