Please wait a minute...
Journal of Integrative Agriculture  2013, Vol. 12 Issue (6): 1073-1078    DOI: 10.1016/S2095-3119(13)60326-3
Animal Science · Veterinary Science Advanced Online Publication | Current Issue | Archive | Adv Search |
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
Download:  PDF in ScienceDirect  
Export:  BibTeX | EndNote (RIS)      
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.
Keywords:  lactic acid       TNF-       IL-6       I B       NF- B  
Received: 09 April 2012   Accepted:
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
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.

[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.
[1] Hyen Chung CHUN, Sanghun LEE, Young Dae CHOI, Dong Hyeok GONG, Ki Youl JUNG. Effects of drought stress on root morphology and spatial distribution of soybean and adzuki bean[J]. >Journal of Integrative Agriculture, 2021, 20(10): 2639-2651.
[2] Leidy J. VALENCIA-HERNÁNDEZ, Karina LÓPEZ-LÓPEZ, Eyder D. GÓMEZ-LÓPEZ, Liliana SERNA-COCK, Cristobal N. AGUILAR . In-vitro assessment for the control of Fusarium species using a lactic acid bacterium isolated from yellow pitahaya (Selenicereus megalanthus (K. Schum. Ex Vaupel Moran))[J]. >Journal of Integrative Agriculture, 2021, 20(1): 159-167.
[3] GUO Gang, SHEN Chen, LIU Qiang, ZHANG Shuan-lin, SHAO Tao, WANG Cong, WANG Yong-xin, XU Qing-fang, HUO Wen-jie.
The effect of lactic acid bacteria inoculums on in vitro rumen fermentation, methane production, ruminal cellulolytic bacteria populations and cellulase activities of corn stover silage
[J]. >Journal of Integrative Agriculture, 2020, 19(3): 838-847.
[4] LI Dong-xia, NI Kui-kui, ZHANG Ying-chao, LIN Yan-li, YANG Fu-yu. Influence of lactic acid bacteria, cellulase, cellulase-producing Bacillus pumilus and their combinations on alfalfa silage quality[J]. >Journal of Integrative Agriculture, 2018, 17(12): 2768-2782.
[5] YIN Ming-ming, ZHU Xin-yan, CHEN Fu-liang. Release performance and sustained-release efficacy of emamectin benzoate-loaded polylactic acid microspheres[J]. >Journal of Integrative Agriculture, 2018, 17(03): 640-647.
[6] Jianbiao Luo, Chaminda Senaka Ranadheera, Stuart King, Craig Evans, Surinder Baines . In vitro investigation of the effect of dairy propionibacteria on rumen pH, lactic acid and volatile fatty acids[J]. >Journal of Integrative Agriculture, 2017, 16(07): 1566-1575.
[7] CHEN Lei, YUAN Xian-jun, LI Jun-feng, WANG Si-ran, DONG Zhi-hao, SHAO Tao. Effect of lactic acid bacteria and propionic acid on conservation characteristics, aerobic stability and in vitro gas production kinetics and digestibility of whole-crop corn based total mixed ration silage[J]. >Journal of Integrative Agriculture, 2017, 16(07): 1592-1600.
[8] LIU Qin-hua, LI Xiang-yu, Seare T Desta, ZHANG Jian-guo, SHAO Tao. Effects of Lactobacillus plantarum and fibrolytic enzyme on the fermentation quality and in vitro digestibility of total mixed rations silage including rape straw[J]. >Journal of Integrative Agriculture, 2016, 15(9): 2087-2096.
[9] NI Kui-kui, YANG Hui-xiao, HUA Wei, WANG Yan-ping, PANG Hui-li. Selection and characterisation of lactic acid bacteria isolated from different origins for ensiling Robinia pseudoacacia and Morus alba L. leaves[J]. >Journal of Integrative Agriculture, 2016, 15(10): 2353-2362.
[10] 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.
[11] LIU Jing-jing, LIU Xiao-ping, REN Ji-wei, ZHAO Hong-yan, YUAN Xu-feng, WANG Xiao-fen, Abdelfattah Z M Salem, CUI Zong-jun. The effects of fermentation and adsorption using lactic acid bacteria culture broth on the feed quality of rice straw[J]. >Journal of Integrative Agriculture, 2015, 14(3): 503-513.
[12] HE Yu-yong, MA Pen, LIU Xiao-lan, WANG Ren-hua , LU Wei. Effect of Different Initial pH on the Storage Characteristics and Shelf Life of Liquid Diet for Suckling and Weanling Piglets[J]. >Journal of Integrative Agriculture, 2014, 13(1): 134-139.
[13] SONG Hui, GAO Jin-feng, GAO Xiao-li, DAI Hui-ping, ZHANG Pan-an, FENG Bai-li, WANG Peng-ke. Relations Between Photosynthetic Parameters and Seed Yields of Adzuki Bean Cultivars (Vigna angularis)[J]. >Journal of Integrative Agriculture, 2012, 12(9): 1453-1461.
[14] ZHAO Xi-an, CANG Ming, GAO Xiao-yu, YANG Mei-ling, YUAN Jian-long, ZHU Bing, WANG Zhi-gang. Expression of Interleukin-6 and Interleukin-6 Receptor in Ovine Oocytes During In vitro Maturation[J]. >Journal of Integrative Agriculture, 2012, 12(8): 1333-1339.
[15] WANG Li-xia, CHENG Xu-zhen, WANG Su-hua, TIAN Jing. Analysis of anApplied Core Collection ofAdzuki Bean Germplasm by Using SSR Markers[J]. >Journal of Integrative Agriculture, 2012, 12(10): 1601-1609.
No Suggested Reading articles found!