Please wait a minute...
Journal of Integrative Agriculture  2015, Vol. 14 Issue (1): 140-147    DOI: 10.1016/S2095-3119(14)60904-7
Animal Science · Veterinary Science Advanced Online Publication | Current Issue | Archive | Adv Search |
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
Download:  PDF in ScienceDirect  
Export:  BibTeX | EndNote (RIS)      
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.
Keywords:  luteolin       neutrophils       phosphodiesterase 4       LFA-1       MAC-1       adhesion       swine  
Received: 23 September 2014   Accepted:
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
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.

Beavo J A. 1995. Cyclic nucleotide phosphodiesterases:Functional implications of multiple isoforms. PhysiologicalReviews, 75, 725-748

Chen C Y, Peng W H, Tsai K D, Hsu S L. 2007. Luteolinsuppresses inflammation-associated gene expression byblocking NF-kappaB and AP-1 activation pathway in mousealveolar macrophages. Life Science, 81, 1602-1614

Chen W, Jiang D X, Yang L, Hu Y, Zhang C X, Yu T Q,Lu Q. 2003. Extraction and activity detection of cAMPphosphodiesterasefrom porcine neutrophils. Journal ofBeijing Agricultural College, 18, 241-244 (in Chinese)

Cheng C Y, Boettcher B. 1982. Partial characterization of humanspermatozoal phosphodiesterase and adenylate cyclaseand the effects of steroids on their activities. InternationalJournal of Andrology, 5, 253-266

Derian C K, Santulli R J, Rao P E, Solomon H F, Barrett J A.1995. Inhibition of chemotactic peptide-induced neutrophiladhesion to vascular endothelium by cAMP modulators.Journal of Immunology, 154, 308-317

Dlaboga D, Hajjhussein H, O’Donnell J M. 2006. Regulation ofphosphodiesterase-4 (PDE4) expression in mouse brainby repeated antidepressant treatment: Comparison withrolipram. Brain Research, 1096, 104-112

Freyer D R, Morganroth M L, Rogers C E, Arnaout M A, Todd IIIR F. 1988. Modulation of surface CD11/CD18 glycoproteins(Mo1, LFA-1, p150, 95) by human mononuclear phagocytes.Clinical Immunological Immunopathology, 46, 272-283

Fujita H, Morita I, Murota S. 1994. A possible mechanismfor vascular endothelial cell injury elicited by activatedleukocytes: A significant involvement of adhesion molecules,CD11/CD18, and ICAM-1. Archives of Biochemistry andBiophysics, 309, 62.

Granger D N, Kubes P. 1994. The microcirculation andinflammation: Modulation of leukocyte-endothelial celladhesion. Journal of Leukocyte Biology, 55, 662.

Jiang D X, Chen W, Gu J N, Xu J Q, Yu T Q, Lu P, Mu X. 2007.Study on activity and gene expression of phosphodiesterasein porcine neutrophils. Scientia Agricultura Sinica, 40,1265-1270 (in Chinese)

Jiang D X, Chen W, Yu T Q, Lu P, Yang L, Mu X. 2006. Preliminarystudy of herbs on the influence of phosphodiesterase 4activity. Journal of Beijing Agricultural College, 21, 7-9

Levallet G, Levallet J, Bonnamy P J. 2008. FSH-inducedphosphoprotein phosphatase 2A-mediated deactivation ofparticulate phosphodiesterase-4 activities is abolished afteralteration in proteoglycan synthesis in immature rat Sertolicells. Journal of Endocrinology, 197, 45-54

 Liu Y, Li J B, Deng X M. 2003. Progress on apoptosis delayingmechanism of neutrophil in inflammatory reaction. ForeignMedical Science (Anesthesilolgy and Resuscitation), 24,190-192

Lugnier C. 2006. Cyclic nucleotide phosphodiesterase (PDE)superfamily: A new target for the development of specifictherapeutic agents. Pharmacology & Therapeutics, 109,366-398

Luo F R, Chen H S. 2000. Neutrophils’ signal transductionpathway of respiratory burst and degranulation. ForeignMedical Science • Section of Pathophysiology ClinicalMedicine, 20, 219-222

Smith C W, Shappel S B. 1994. Acute inflammatory response:Granulocyte migration and activation. In: The Handbookof Immunophamacology: Adhesion Molecules. AcademicPress, San Diego. pp. 29-70

Torphy T J. 1998. Phosphodiesterase isozymes: Moleculartargets for novel antiasthma agents. American Journal ofRespiratory and Critical Care Medicine, 157, 351-370

Wang J S, He Y, Zhang W J, Zhang P, Huang Q L, Hua Z C.2013. Advances in studies on pharmacological effects ofluteolin. Chinese Bulletin of Life Science, 25, 560-565 (inChinese)

Wang P, Wu P, Ohleth K M, Egan R W, Billah M M.1999. Phosphodiesterase 4B2 is the predominantphosphodiesterase species and undergoes differentialregulation of gene expression in human monocytes andneutrophils. Molecular Pharmacology, 56, 170-174

Wheeler M A, Ayyagari R R, Wheeler G L, Weiss R M. 2005.Regulation of cyclic nucleotides in the urinary tract. Journalof Smooth Muscle Research, 41, 1-21

Zarbock A, Ley K. 2008. Mechanisms and consequencesof neutrophil interaction with the endothelium. AmericanJournal of Pathology, 172, 1-7

Zhu L H, Bi W, Qi R B, Wang H D, Lu D X. 2011. Luteolin inhibitsmicroglial inflammation and improves neuron survivalagainst inflammation. International Journal of Neuroscience,121, 329-336
[1] SONG Xiang-peng, XIA Ying-ju, XU Lu, ZHAO Jun-jie, WANG Zhen, ZHAO Qi-zu, LIU Ye-bing, ZHANG Qian-yi, WANG Qin. A multiplex real-time PCR assay for simultaneous detection of classical swine fever virus, African swine fever virus and atypical porcine pestivirus[J]. >Journal of Integrative Agriculture, 2023, 22(2): 559-567.
[2] GUO Shi-juan, LÜ Xin-ye, HU Xiang-dong. Optimal design of culling compensation policy under the African swine fever — Based on simulations of typical pig farms in China[J]. >Journal of Integrative Agriculture, 2023, 22(2): 611-622.
[3] WANG Peng-fei, WANG Ming, SHI Zhi-bin, SUN Zhen-zhao, WEI Li-li, LIU Zai-si, WANG Shi-da, HE Xi-jun, WANG Jing-fei. Development of a recombinant pB602L-based indirect ELISA assay for detecting antibodies against African swine fever virus in pigs[J]. >Journal of Integrative Agriculture, 2022, 21(3): 819-825.
[4] XIE Xing,  HAO Fei, WANG Hai-yan, PANG Mao-da, GAN Yuan, LIU Bei-bei, ZHANG Lei, WEI Yan-na, CHEN Rong, ZHANG Zhen-zhen, BAO Wen-bin, BAI Yun, SHAO Guo-qing, XIONG Qi-yan, FENG Zhi-xin. Construction of a telomerase-immortalized porcine tracheal epithelial cell model for swine-origin mycoplasma infection[J]. >Journal of Integrative Agriculture, 2022, 21(2): 504-520.
[5] LI Hui-shang, HU Chen-pei, LÜ Zheng, LI Mei-qi, GUO Xin-zhu. African swine fever and meat prices fluctuation: An empirical study in China based on TVP-VAR model[J]. >Journal of Integrative Agriculture, 2021, 20(8): 2289-2301.
[6] WANG Zi-lin, FENG Ke-ying, GE Xiu-feng, MAI Jia-cheng, WANG Han-chuan, LIU Wen-zi, ZHANG Jia-hui, SHEN Xiang-guang. Effects of 105 traditional Chinese medicines on the detection of β-agonists in medicine extracts and swine urine based on colloidal gold immunochromatographic assay[J]. >Journal of Integrative Agriculture, 2021, 20(6): 1626-1635.
[7] JIANG Cheng-gang, SUN Ying, ZHANG Fan, AI Xin, FENG Xiao-ning, HU Wei, ZHANG Xian-feng, ZHAO Dong-ming, BU Zhi-gao, HE Xi-jun. Viricidal activity of several disinfectants against African swine fever virus[J]. >Journal of Integrative Agriculture, 2021, 20(11): 3084-3088.
[8] WANG Jun, SHI xin-jin, SUN Hai-wei, CHEN Hong-jun. Insights into African swine fever virus immunoevasion strategies[J]. >Journal of Integrative Agriculture, 2020, 19(1): 11-22.
[9] Xiao Wu, Jun Zhu, Hongjian Lin. In-depth observations of fermentative hydrogen production from liquid swine manure using an anaerobic sequencing batch reactor[J]. >Journal of Integrative Agriculture, 2017, 16(06): 1276-1285.
[10] ZHANG Zhe, ZHANG Hao, PAN Rong-yang, WU Long, LI Ya-lan, CHEN Zan-mou, CAI Geng-yuan, LI Jia-qi, WU Zhen-fang. Genetic parameters and trends for production and reproduction traits of a Landrace herd in China[J]. >Journal of Integrative Agriculture, 2016, 15(05): 1069-1075.
[11] WEI Yan-di, PEI Xing-yao, ZHANG Yuan, YU Chen-fang, SUN Hong-lei, LIU Jin-hua, PU Juan. Nested RT-PCR method for the detection of European avian-like H1 swine influenza A virus[J]. >Journal of Integrative Agriculture, 2016, 15(05): 1095-1102.
[12] JIANG Dai-xun, ZHANG Mei-hua, ZHANG Qian, CHEN Yi-shan, MA Wen-jing, WU Wei-peng, MU Xiang. Influence of gallic acid on porcine neutrophils phosphodiesterase 4, IL-6, TNF-α and rat arthritis model[J]. >Journal of Integrative Agriculture, 2015, 14(4): 758-764.
[13] DENG Xian-bai, DIN Huan-zhong, HUANG Xian-hui, MA Yong-jiang, FAN Xiao-long, YAN Hai-kuo, LU Pei-cheng, LI Wei-cheng, ZENG Zhen-ling. Tissue distribution of deoxynivalenol in piglets following intravenous administration[J]. >Journal of Integrative Agriculture, 2015, 14(10): 2058-2064.
[14] HUANG Jun-hua, LI Yong-feng, HE Fan, LI Dan, SUN Yuan, HAN Wen , QIU Hua-ji. Rapid Recovery of Classical Swine Fever Virus Directly from Cloned cDNA[J]. >Journal of Integrative Agriculture, 2013, 12(5): 877-883.
[15] ZHAO Ning, WANG Lin, LU Xiao-xiong, JIA Hui-qin, FANG Bing-hu, ZENG Zhen-ling , DING Huanzhong. Pharmacokinetics of Cyadox and Its Major Metabolites in Swine After Intravenous and Oral Administration[J]. >Journal of Integrative Agriculture, 2013, 12(3): 495-501.
No Suggested Reading articles found!