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Luteolin prevents fMLP-induced neutrophils adhesion via suppression of LFA-1 and phosphodiesterase 4 activity |
JIANG Dai-xun, LIU Shu-rong, ZHANG Mei-hua, ZHANG Tao, MA Wen-jing, MU Xiang, CHEN Wu |
Beijing Key Laboratory of Traditional Chinese Veterinary Medicine, Beijing University of Agriculture, Beijing 102206, P.R.China |
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摘要 Luteolin is an active ingredient found early from Folium perillae and Flos lonicerae, and has a specific inhibition on phosphodiesterase 4 (PDE4) activity in vitro. Researches show luteolin has pharmacological effects of anti-inflammation, anti-anaphylaxis, antitumor, antioxidant, protection of nervous system and so on, and has mainly been used for the treatment of respiratory inflammatory diseases, cancer and cardiovascular disease in clinic. PDE4, specific to hydrolyze cyclic AMP (cAMP), is considered to be a new anti-inflammatory target due to the decisive role on cAMP signal in inflammatory cells such as neutrophils. In order to explore the anti-inflammatory mechanism, we further studied the effects of luteolin on the activity and expression of PDE4, the expression of lymphocyte function-associated antigen-1 (LFA-1) and macrophage-1 (MAC-1) in neutrophils, and the adhesion of neutrophils and endothelial cells. The results showed that luteolin had a dose-dependent inhibition on both bare PDE4 activity and PDE4 in cultured neutrophils, and had an obviously promotive effect on gene expressions of PDE4A, 4B and 4D in later period. Luteolin had a significant inhibitory effect on neutrophils adhesion and LFA-1 expression in early stage, and had no obvious effect on MAC-1 expression. Therefore, luteolin can inhibit LFA-1 expression of neutrophils, then inhibit the adhesion of neutrophils and endothelial cells, and the mechanism is at least related with the inhibition of PDE4 activity.
Abstract Luteolin is an active ingredient found early from Folium perillae and Flos lonicerae, and has a specific inhibition on phosphodiesterase 4 (PDE4) activity in vitro. Researches show luteolin has pharmacological effects of anti-inflammation, anti-anaphylaxis, antitumor, antioxidant, protection of nervous system and so on, and has mainly been used for the treatment of respiratory inflammatory diseases, cancer and cardiovascular disease in clinic. PDE4, specific to hydrolyze cyclic AMP (cAMP), is considered to be a new anti-inflammatory target due to the decisive role on cAMP signal in inflammatory cells such as neutrophils. In order to explore the anti-inflammatory mechanism, we further studied the effects of luteolin on the activity and expression of PDE4, the expression of lymphocyte function-associated antigen-1 (LFA-1) and macrophage-1 (MAC-1) in neutrophils, and the adhesion of neutrophils and endothelial cells. The results showed that luteolin had a dose-dependent inhibition on both bare PDE4 activity and PDE4 in cultured neutrophils, and had an obviously promotive effect on gene expressions of PDE4A, 4B and 4D in later period. Luteolin had a significant inhibitory effect on neutrophils adhesion and LFA-1 expression in early stage, and had no obvious effect on MAC-1 expression. Therefore, luteolin can inhibit LFA-1 expression of neutrophils, then inhibit the adhesion of neutrophils and endothelial cells, and the mechanism is at least related with the inhibition of PDE4 activity.
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Received: 23 September 2014
Accepted:
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Fund: We gratefully acknowledge the financial support of the Beijing Natural Science Foundation, China (6112007), the National Natural Science Foundation of China (31101851), the Funding Project for Academic Human ResourcesDevelopment in Institutions of Higher Learning under the Jurisdiction of Beijing Municipality, China (PHR201107134), and the Comprehensive Reforming Project to promote talents training of Beijing University of Agriculture, China (BNRC&GG201404). |
Corresponding Authors:
CHEN Wu, Tel/Fax: +86-10-80799434, E-mail: tcvmchenwu@hotmail.com
E-mail: tcvmchenwu@hotmail.com
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About author: JIANG Dai-xun, Tel/Fax: +86-10-80793027, E-mail: dx_tcvm@126.com;* These authors contributed equally to this study. |
Cite this article:
JIANG Dai-xun, LIU Shu-rong, ZHANG Mei-hua, ZHANG Tao, MA Wen-jing, MU Xiang, CHEN Wu.
2015.
Luteolin prevents fMLP-induced neutrophils adhesion via suppression of LFA-1 and phosphodiesterase 4 activity. Journal of Integrative Agriculture, 14(1): 140-147.
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