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:: Volume 28, Issue 4 (10-2020) ::
Journal of Ilam University of Medical Sciences 2020, 28(4): 12-24 Back to browse issues page
L-Glutamin-Induced Inhibition of Endotoxemia by Reducing Pre-Inflammatory Cytokines, Nitric Oxide, and CD40 Expression
Yaser Jafari khataylou * 1, Somayeh Ahmadiafshar2
1- Dept of Pathobiology, Faculty of Veterinary medicine, University of Tabriz, Tabriz, Iran , y.jafari@tabrizu.ac.ir
2- Dept of Microbiology, Faculty of Veterinary medicine, University of Urmia, Urmia, Iran
Abstract:   (1879 Views)
Introduction: Researchers have been investigating the major pathogens involved in septic shock caused by lipopolysaccharide in recent years. Moreover, they have been concerned about the use of appropriate drugs to intervene with the main pathogenesis of the disease. This study aimed to investigate the effect of L-Glutamine as an HSP70 inducer in reducing pre-inflammatory cytokines and effective intermediaries in septic shock, including nitric oxide production and CD40 expression in mice treated with lipopolysaccharide (LPS).
Materials & Methods: In total, 25 Swiss Albino mice were randomly divided into three groups of A (control group, n=5), (received LPS with a dose of 0.75 mg/animal intraperitoneally [IP], (n=10), and (received L-glutamine with a dose of 50 mg/kg IP 30 minutes after the injection of LPS [three doses every 24 h], (n=10). Subsequently, one day after the final dose of drug induction, the number of cytokines, such as IFN-γ, IL-4, IL-10, HSP70, CD40, and nitric oxide, were evaluated in this study. Ethics code: IR.TABRIZU.REC.1398.003
Findings: The data were analyzed in SPSS software (version 19) through a one-way analysis of variance and Scheffe test. According to the results, L-glutamine can significantly reduce the serum levels of pre-inflammatory cytokine, nitric oxide, and CD40 expression in the drug-treated group (group C), compared to the LPS- treated group (group B) (P<0.05).
Discussions & Conclusions: L-glutamine could be a good choice for treatment by reducing the level of inflammatory mediators.
Keywords: Heat shock protein70, L-glutamine, Lipopolysaccharide, Nitric oxide
Full-Text [PDF 1058 kb]   (780 Downloads)    
Type of Study: Research | Subject: immunology
Received: 2019/12/18 | Accepted: 2020/05/26 | Published: 2020/10/31
1. Kobayashi M, Tsuda Y, Yoshida T, Takeuchi D, Utsunomiya T, Takahashi H, et al. Bacterial sepsis and chemokines. Curr Drug Targ 2006; 7: 119-34. doi. 10.2174/138945006775270169
2. Marino LV, Pathan N, Meyer R, Wright V, Habibi P. Glutamine depletion and heat shock protein 70 in children with meningococcal disease. Clin Nutr 2014; 33:915-21. doi.10.1016/j.clnu.2013.09.013
3. Wang Y, Kelly CG, Karttunen JT, Whittall T, Lehner PJ, Duncan L, et al. CD40 is a cellular receptor mediating mycobacterial heat shock protein 70 stimulation of CC-chemokines. Immunity 2001; 15:971-83. doi.10.1016/S1074-7613(01)00242-4
4. Ramana KV, Fadl AA, Tammali R, Reddy AB, Chopra AK, Srivastava SK. Aldose reductase mediates the lipopolysaccharide induced release of inflammatory mediators in RAW264.7 murine macrophages. J Biol Chem 2006 Nov 3;281:33019-29. doi. 10.1074/jbc.M603819200.
5. Newsholme EA, Parry M. Properties of glutamine release from muscle and its importance for the immune system J Par Ent Nutr1990;14:63-7. doi. 10.1177/014860719001400406.
6. Ko HM, Oh SH, Bang HS, Kang NI, Cho BH, Im SY, et al. Glutamine protects mice from lethal endotoxic shock via a rapid induction of MAPK phosphatase-1. J Immunol 2009; 182:7957-62. doi.10.4049/jimmunol.0900043.
7. Carrillo A, Lardone PJ, Naji L, Fernandez JM, Martin I, Guerrero JM, et al. Beneficial pleiotropic actions of melatonin in an experimental model of septic shock in Mice regulation of pro-/anti-inflammatory cytokine network, protection against oxidative damage and anti-apoptotic effects. J Pineal Res 2005; 39: 400-408. doi.10.1111/j.1600-079X.2005.00265. x.
8. Jafarikhatailou Y, Delirezh N, Farshid AA, Zafarshamspoor S, Shahabi SH. Effect of L-Glutamine on fasting blood sugar and pathological lesions of autoimmune diabetes in male C57BL/6 mice. Stud Med Sci 2012; 23:133-40.
9. Mishra KP, Rani R, Yadav VS, Naik S. Effect of lead exposure on lymphocyte subsets and activation markers. Immunopharmacol Immunotoxicol 2010; 32:446-9. doi.10.3109/08923970903503668.
10. Azadmehr A, Afshari A, Baradaran B, Hajiaghaee R, Rezazadeh SH, Monsefesfahani H. Suppression of nitric oxide production in activated murine peritoneal macrophages in vitro and ex vivo by scrophularia striata ethanolic extract. Ethnopharmacol 2009; 124:166-169. doi.10.1016/j.jep.2009.03.042
11. Guzik TJ, Korbut R, Adamek T. Nitric oxide and superoxide in inflammation and immune regulation. J Physiol Pharmacol, :469-87.
12. Lindros KO, Jarvelainen HA. Chronic systemic endotoxin exposure an animal model in experimental hepatic encephalopathy. Metab Brain Dis2005; 20: 393-8. doi.10.1007/s11011-005-7924-2.
13. Oliveira GP, Dias CM, Pelosi P, Rocco PR. Understanding the mechanisms of glutamine action in critically ill patients. An Acad Bras Cienc 2010; 82:417-30. doi.10.1590/s0001-37652010000200018.
14. Lecleire S, Hassan A, Marion R, Antonietti M, Savoye G, Bole C, et al. Combined glutamine and arginine decrease proinflammatory cytokine production by biopsies from Crohns patients in association with changes in nuclear factor kappaB and p38 mitogen activated protein kinase pathways. J Nutr 2008; 138:2481-6. doi. 10.3945/jn.108.099127.
15. Cruzat V, Macedo M, Noel K, Curi R, Newsholme P. Glutamine metabolism and immune function, supplementation and clinical translation. Nutrients 2018; 23:10. doi.10.3390/nu10111564.
16. Jacque N, Ronchetti AM, Larrue C, Meunier G, Birsen R, Willems L, et al. Targeting glutaminolysis has antileukemic activity in acute myeloid leukemia and synergizes with BCL-2 inhibition. Blood 2015; 126:1346-56. doi.10.1182/blood-2015-01-621870.
17. Xuefeng W, Lei H, Yanxia Qu, Hongmei Lv, Xiaohua He. Effects of glutamine on cytokines 1L-1 and TNF-α in rehabilitation and prognosis of patients with lobectomy. Exp Ther Med. 2018; 16: 2303-08. doi.10.3892/etm.2018.6443
18. Ferat E, Sanchez A, Gutierrez M, Bosco I, Wong I, Pastelin R, et al. Heat shock protein 70 down regulates the production of toll like receptor induced pro inflammatory cytokines by a heat shock factor-1/constitutive heat shock element binding factor dependent mechanism. J Inflamm 2014; 12; 11:19. doi.10.1186/1476-9255-11-19.
19. Barquera C, Rivera RRy. Obesidad en Mexico epidemiologia y politicas de salud para su control y prevencion. Gac Med Mex 2010; 146:397-407.
20. Luo X, Zuo X, Mo X, Zhou Y, Xiao X. Treatment with recombinant Hsp72 suppresses collagen induced arthritis in Mice. Inflammation 2011; 34:432-9.
21. Bangen JM, Schade FU, Flohe SB. Diverse regulatory activity of human heat shock proteins 60 and 70 on endotoxin induced inflammation. Biochem Biophys Res Commun2007; 359:709-15. doi.10.1016/j.bbrc.2007.05.167.
22. Becker T, Hartl FU, Wieland F. CD40 an extracellular receptor for binding and uptake of Hsp70 peptide complexes. J Cell Biol 2002; 30; 158:1277-85. dol: 10.1083/ jcb.200208083.
23. Zitvogel L, Kepp O, Kroemer G. Decoding cell death signals in inflammation and immunity. Cell 2010; 109: 4839-45. doi.10.1016/j.cell.2010.02.015
24. Dalpke A, Zimmermann S, Heeg K. CpG DNA in the Prevention and treatment of infections. Biodrugs 2002; 16: 419-31. doi.10.2165/00063030-200216060-00003.
25. Bryk J, Ochoa JB, Correia MI, Munera V, Popovic PJ. Effect of citrulline and glutamine on nitric oxide production in RAW 264.7 cells in an arginine depleted environment. J Parent Ent Nutr 2008; 32:377-83. doi.10.1177/0148607108319807.
26. Zanin A, Nussbaum G, Franitza S, Cohen IR, Lider O. T cells respond to heat shock protein 70 via TLR4 activation of adhesion and inhibition of chemokine receptors. Faseb J 2003; 17:1567-9. doi.10.1096/fj.02-1139fje
27. Hayashi Y, Sawa Y, Fukuyama N, Nakazawa H, Matsuda H. Preoperative glutamine administration induces heat shock protein 70 expression and attenuates cardiopulmonary bypass induced inflammatory response by regulating nitric oxide synthase activity. Circulation 2002; 106:2601-7. doi. 10.1161/01.cir.0000035651.72240.07.
28. Tone M, Tone Y, Babik JM, Lin CY, Waldmann H. The role of sp1 and NF-κB in regulating CD40 gene expression. J Biol Chem2002; 277:8890-7. doi.10.1074/ jbc.m109889200
29. Jong YP, Comiskey M, Kalled SL, Mizoguchi E, Flavell RA, Bhan AK, et al. Chronic murine colitis is dependent on the CD154/CD40 pathway and can be attenuated by anti-CD154 administration. Gastroenterology 2000; 119:715-23. doi.10.1053/gast.2000.16485
30. Pullen SS, Dang TT, Crute JJ, Kehry MR. CD40 signaling through tumor necrosis factor receptor-associated factors. Binding site specificity and activation of downstream pathways by distinct TRAFs. J Biol Chem 1999; 274:14246-54. doi. 10.1074/jbc.274.20.14246.
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Ethics code: IR.TABRIZU.REC.1398.003

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Jafari khataylou Y, Ahmadiafshar S. L-Glutamin-Induced Inhibition of Endotoxemia by Reducing Pre-Inflammatory Cytokines, Nitric Oxide, and CD40 Expression. Journal of Ilam University of Medical Sciences 2020; 28 (4) :12-24
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Volume 28, Issue 4 (10-2020) Back to browse issues page
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