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Lactic Acid Reduces LPS-Induced TNF- and IL-6 mRNA Levels Through Decreasing I B Phosphorylation |
XU Guang-yong, JIANG Jin-qi, WANG Ming, LI Jie, SU Jing-liang , REN Xiao-ming |
1 Animal Science and Technology College, Beijing University of Agriculture, Beijing 102206, P.R.China
2 Beijing Key Laboratory of Traditional Chinese Veterinary Medicine, Beijing University of Agriculture, Beijing 102206, P.R.China
3 College of Veterinary Medicine, China Agricultural University, Beijing 100193, P.R.China |
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摘要 This study explored the effects over time of lactic acid (LA) on I Bα phosphorylation and nuclear factor-kappa B (NF- B) p65 protein expression, and on tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) mRNA levels in rat intestinal mucosa microvascular endothelial cells (RIMMVECs) stimulated by lipopolysaccharide (LPS). I B , phosphorylated I B (p-I B ) and p65 protein levels were monitored by Western blot analysis, and TNF- and IL-6 mRNA levels were analyzed using real-time PCR. LA treatment reduced TNF- and IL-6 mRNA levels in LPS-stimulated RIMMVECs, with the greatest effect being after 3 h. The highest inhibitory effect of LA on I B phosphorylation to prevent activation of NFB was after 6 h. These results suggest that LA reduces TNF- and IL-6 mRNA levels through decreasing I B phosphorylation and blocking the dissociation of IKK complex, which prevents activation of NF- B.
Abstract This study explored the effects over time of lactic acid (LA) on I Bα phosphorylation and nuclear factor-kappa B (NF- B) p65 protein expression, and on tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) mRNA levels in rat intestinal mucosa microvascular endothelial cells (RIMMVECs) stimulated by lipopolysaccharide (LPS). I B , phosphorylated I B (p-I B ) and p65 protein levels were monitored by Western blot analysis, and TNF- and IL-6 mRNA levels were analyzed using real-time PCR. LA treatment reduced TNF- and IL-6 mRNA levels in LPS-stimulated RIMMVECs, with the greatest effect being after 3 h. The highest inhibitory effect of LA on I B phosphorylation to prevent activation of NFB was after 6 h. These results suggest that LA reduces TNF- and IL-6 mRNA levels through decreasing I B phosphorylation and blocking the dissociation of IKK complex, which prevents activation of NF- B.
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Received: 09 April 2012
Accepted:
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Fund: This study was supported by the Natural Science Foundation of Beijing, China (6072007), and the Project for the Establishment and Development of Swine Disease Clinical Diagnosis, China (KM200910020002). |
Corresponding Authors:
Correspondence REN Xiao-ming, Tel/Fax: +86-10-80795532, E-mail: xm-ren@163.com;SU Jing-liang, Tel/Fax: +86-10-62732312, E-mail: jinglsu@yahoo.com
E-mail: xm-ren@163.com
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About author: XU Guang-yong, Mobile: 15210922015, E-mail: 15210922015@139.com |
Cite this article:
XU Guang-yong, JIANG Jin-qi, WANG Ming, LI Jie, SU Jing-liang , REN Xiao-ming.
2013.
Lactic Acid Reduces LPS-Induced TNF- and IL-6 mRNA Levels Through Decreasing I B Phosphorylation. Journal of Integrative Agriculture, 12(6): 1073-1078.
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[1]Ahn K S, Aggarwal B B. 2005. Transcription factor NFkappaB:asensor for smoke and stress signals. Annalsof the New York Academy of Sciences, 1056, 218-233[2]le Bail O, Schmidt-Ullrich R, Israel A. 1993. Promoteranalysis of the gene encoding the IkappaB-alpha/MAD3 inhibitor of NF-kappa B: positive regulation bymembers of the rel/NF-kappa B family. EMBO Journal,12, 5043-5049[3]Collart M A, Baeuerle P, Vassalli P. 1990. Regulation oftumor necrosis factor alpha transcription inmacrophages: involvement of four kappa B-like motifsand of constitutive and inducible forms of NF-kappa B.Molecular and Cellular Biochemistry, 10, 1498-1506[4]Collins T, Read M A, Neish A S, Whitley M Z, Thanos D,Maniatis T. 1995. Transcriptional regulation ofendothelial cell adhesion molecules: NF-?B and cytokine-inducible enhancers. FASEB Journal, 9, 899-909[5]Cordle S R, Donald R, Read M A, Hawiger J. 1993.Lipopolysaccharide induces phosphorylation of MAD3and activation of c-Rel and related NF-?B proteins inhuman monocytic THP-1 cells Journal of BiologicalChemistry, 268, 11803-11810[6]Deshpande R, Khalili H, Pergolizzi R G, Michael S D, ChangM D. 1997. Estradiol down-regulates LPS-inducedcytokine production and NF-?B activation in murinemacrophages. American Journal of ReproductiveImmunology, 38, 46-54[7]DiDonato J A, Hayakawa M, Rothwarf D M, Zandi E, KarinM. 1997. A cytokine-responsive IkappaB kinase thatactivates the transcription factor NF-kappaB. Nature,388, 548-554[8]Eder K, Baffy N, Falus A, Fulop A K. 2009. The majorinflammatory Mediator interleukin-6 and obesity[9]Inflammation Research, 58, 727-736[10]Galien R, Evans H F, Garcia T. 1996. Involvement of CCAAT/enhancer-binding protein and nuclear factor-kappa Bbinding sites in interleukin-6 promoter inhibition byestrogens Molecular Endocrinology, 10, 713-722[11]Hayden M S, Ghosh S. 2008. Shared principles in NF-kappaBsignaling pathways. Cell, 132, 344-362[12]Hindryckx P, de Vos M, Jacques P, Ferdinande L, PeetersH, Olievier K, Bogaert S, Brinkman B, Vandenabeele P,Elewaut D, et al. 2010. Hydroxylase inhibition abrogatesTNF-a induced intestinal epithelial damage by hypoxiainduciblefactor-1-dependent repression of FADD TheJournal of Immunology, 185, 6306-6316[13]Kishimoto T. 2010. IL-6: from its discovery to clinicalapplications International Immunology, 22, 347-352[14]Kumar A, Takada Y, Boriek A M, Aggarwal B B. 2004. Nuclearfactor-kappaB: its role in health and disease. TheJournal of Molecular Medicine, 82, 434-448[15]Liu J, Xue J Z, Zhu Z N, Hu G, Ren X M. 2011. Lactic acidinhibits NF-?B activation by lipopolysaccharide in ratintestinal mucosa microvascular endothelial cells.Agricultural Sciences in China, 10, 954-959[16]Lee J M, Hwang K T, Jun W J, Park C S, Lee M Y. 2008.Antiinflammatory effect of lactic acid bacteria:inhibition of cyclooxygenase-2 by suppressing nuclearfactor-?B in Raw2647 macrophage cells. Journal ofMicrobiology and Biotechnology, 18, 1683-1688[17]de Luc V, Frederic L. 2007. Bacteriocins from lactic acidbacteria: production, purification, and food applications.J o u r n a l o f M o l e c u l a r M i c r o b i o l o g y a n dBiotechnology, 13, 194-199[18]Mercurio F, Zhu H, Murray B W, Shevchenko A, BennettB L, Li J. 1997. IKK-1 and IKK-2: cytokine-activatedIkappaB kinases essential for NF-kappaB activation Science, 278, 860-866[19]Odrowaz-Sypniewska G. 2007. Markers of pro-inflammatoryand pro-thrombotic state in the diagnosis of metabolicsyndrome. Advances in Medical Sciences, 52, 246-250[20]Sun D, Lytle C, O´Donnell M E. 1997. IL-6 secreted byastroglial cells regulates Na-K-Cl cotransport in brainmicrovessel endothelial cells American Journal ofPhysiology, 272, C1829-C1835.[21]Tabruyn S P, Mémet S, Avé P, Verhaeghe C, Mayo K H,Struman I, Martial J A, Griffioen A W. 2009. NF-?Bactivation in endothelial cells is critical for the activityof angiostatic agents. Molecular Cancer Therapeutics,8, 2645-2654[22]Zandi E, Rothwarf D M, Delhase M, Hayakawa M, KarinM. 1997. The IkappaB kinase complex (IKK) containstwo kinase subunits, IKKalpha and IKKbeta, necessaryfor IkappaB phosphorylation and NF-kappaBactivation. Cell, 91, 243-252[23]Zhang Y H, Lian F Z, Zhu Y N, Xia M, Wang Q, Ling W H,Wang X D. 2010. Cyanidin-3-O-?-glucooside inhibitsLPS-induced expression of inflammatory mediatorsthrough decreasing I?B??phosphorylation in THP-1cells Inflammation Research, 59, 723-730. |
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