L-carnitine, a diet component and organic cation transporter OCTN ligand, displays immunosuppressive properties and abrogates intestinal inflammation

Clinical and Experimental Immunology

Volumn 156, Issue 1, 2009, Pages 161-171

  Fortin, G ^a,b   Yurchenko, K ^c   Collette, C ^b   Rubio, M ^d   Villani, A C ^b   Bitton, A ^b   Sarfati, M ^d   Franchimont, D ^b  

^a MONTREAL GENERAL HOSPITAL   (Canada)

^b MCGILL UNIVERSITY HEALTH CENTRE   (Canada)

^c MCGILL UNIVERSITY   (Canada)

^d CENTRE HOSPITALIER DE L UNIVERSITÉ DE MONTRÉAL   (Canada)

Author keywords

Antigen presenting cells; Carnitine; Crohn's disease; T lymphocytes; Trinitrobenzene sulphonic acid colitis

Indexed keywords

CARNITINE; INTERLEUKIN 1BETA; INTERLEUKIN 6; ORGANIC CATION TRANSPORTER; TRINITROBENZENESULFONIC ACID;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIGEN PRESENTING CELL; ARTICLE; CD4+ T LYMPHOCYTE; CELL CULTURE; CELL FUNCTION; CELL PROLIFERATION; CELLULAR IMMUNITY; COLITIS; CONTROLLED STUDY; CYTOKINE PRODUCTION; DENDRITIC CELL; DRUG EFFICACY; IMMUNE RESPONSE; IMMUNOMODULATION; IMMUNOSUPPRESSIVE TREATMENT; INNATE IMMUNITY; LYMPHOCYTE FUNCTION; MACROPHAGE FUNCTION; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION;

ANIMALS; CARNITINE; CD4-POSITIVE T-LYMPHOCYTES; CELLS, CULTURED; COLITIS; CYTOKINES; DENDRITIC CELLS; DIETARY SUPPLEMENTS; DISEASE MODELS, ANIMAL; DOSE-RESPONSE RELATIONSHIP, IMMUNOLOGIC; DRUG EVALUATION, PRECLINICAL; IMMUNOSUPPRESSIVE AGENTS; INFLAMMATION MEDIATORS; LIPOPOLYSACCHARIDES; LYMPHOCYTE ACTIVATION; MACROPHAGES; MALE; MICE; MICE, INBRED BALB C; ORGANIC CATION TRANSPORT PROTEINS; SPLEEN; TRINITROBENZENESULFONIC ACID;

EID: 61849152432     PISSN: 00099104     EISSN: 13652249     Source Type: Journal    
DOI: 10.1111/j.1365-2249.2009.03879.x     Document Type: Article

References (44)

1. Elson CO, Sartor RB, Tennyson GS, Riddell RH. Experimental models of inflammatory bowel disease. Gastroenterology 1995 109 : 1344 67.
2. Fujino S, Andoh A, Bamba S et al. Increased expression of interleukin 17 in inflammatory bowel disease. Gut 2003 52 : 65 70.
3. Schmidt C, Giese T, Ludwig B et al. Expression of interleukin-12-related cytokine transcripts in inflammatory bowel disease: elevated interleukin-23p19 and interleukin-27p28 in Crohn's disease but not in ulcerative colitis. Inflamm Bowel Dis 2005 11 : 16 23.
4. Tobin MV, Logan RF, Langman MJ, McConnell RB, Gilmore IT. Cigarette smoking and inflammatory bowel disease. Gastroenterology 1987 93 : 316 21.
5. Evans JM, McMahon AD, Murray FE, McDevitt DG, MacDonald TM. Non-steroidal anti-inflammatory drugs are associated with emergency admission to hospital for colitis due to inflammatory bowel disease. Gut 1997 40 : 619 22.
6. Duffy LC, Zielezny MA, Marshall JR et al. Relevance of major stress events as an indicator of disease activity prevalence in inflammatory bowel disease. Behav Med 1991 17 : 101 10.
7. Levi AJ. Diet in the management of Crohn's disease. Gut 1985 26 : 985 8.
8. Hartman C, Berkowitz D, Weiss B et al. Nutritional supplementation with polymeric diet enriched with transforming growth factor-beta 2 for children with Crohn's disease. Isr Med Assoc J 2008 10 : 503 7.
9. Rebouche CJ, Seim H. Carnitine metabolism and its regulation in microorganisms and mammals. Annu Rev Nutr 1998 18 : 39 61.
10. Wu X, Huang W, Prasad PD et al. Functional characteristics and tissue distribution pattern of organic cation transporter 2 (OCTN2), an organic cation/carnitine transporter. J Pharmacol Exp Ther 1999 290 : 1482 92.
11. Rebouche CJ, Engel AG. Tissue distribution of carnitine biosynthetic enzymes in man. Biochim Biophys Acta 1980 630 : 22 9.
12. Rebouche CJ. Carnitine function and requirements during the life cycle. FASEB J 1992 6 : 3379 86.
13. Fritz IB, Marquis NR. The role of acylcarnitine esters and carnitine palmityltransferase in the transport of fatty acyl groups across mitochondrial membranes. Proc Natl Acad Sci USA 1965 54 : 1226 33.
14. Peltekova VD, Wintle RF, Rubin LA et al. Functional variants of OCTN cation transporter genes are associated with Crohn disease. Nat Genet 2004 36 : 471 5.
15. Vermeire S, Pierik M, Hlavaty T et al. Association of organic cation transporter risk haplotype with perianal penetrating Crohn's disease but not with susceptibility to IBD. Gastroenterology 2005 129 : 1845 53.
16. Van Limbergen J, Russell RK, Nimmo ER, Satsangi J. The genetics of inflammatory bowel disease. Am J Gastroenterol 2007 102 : 2820 31.
17. Shekhawat PS, Srinivas SR, Matern D et al. Spontaneous development of intestinal and colonic atrophy and inflammation in the carnitine-deficient jvs (OCTN2(-/-)) mice. Mol Genet Metab 2007 92 : 315 24.
18. D'Argenio G, Calvani M, Casamassimi A et al. Experimental colitis: decreased Octn2 and Atb0+ expression in rat colonocytes induces carnitine depletion that is reversible by carnitine-loaded liposomes. FASEB J 2006 20 : 2544 6.
19. Winter BK, Fiskum G, Gallo LL. Effects of L-carnitine on serum triglyceride and cytokine levels in rat models of cachexia and septic shock. Br J Cancer 1995 72 : 1173 9.
20. Athanassakis I, Mouratidou M, Sakka P, Evangeliou A, Spilioti M, Vassiliadis S. L-carnitine modifies the humoral immune response in mice after in vitro or in vivo treatment. Int Immunopharmacol 2001 1 : 1813 22.
21. Fattorossi A, Biselli R, Casciaro A, Tzantzoglou S, de Simone C. Regulation of normal human polyrnorphonuclear leucocytes by carnitine. Mediators Inflamm 1993 2 : S37 41.
22. Alesci S, De Martino MU, Mirani M et al. A nutritional modulator of glucocorticoid receptor functions. FASEB J 2003 17 : 1553 5.
23. Kouttab NM, De Simone C. Modulation of cytokine production by carnitine. Mediators Inflamm 1993 2 : S25 8.
24. De Simone C, Ferrari M, Meli D, Midiri G, Sorice F. Reversibility by L-carnitine of immunosuppression induced by an emulsion of soya bean oil, glycerol and egg lecithin. Arzneimittelforschung 1982 32 : 1485 8.
25. De Simone C, Famularo G, Tzantzoglou S, Trinchieri V, Moretti S, Sorice F. Carnitine depletion in peripheral blood mononuclear cells from patients with AIDS: effect of oral L-carnitine. AIDS 1994 8 : 655 60.
26. Dohi T, Fujihashi K, Rennert PD, Iwatani K, Kiyono H, McGhee JR. Hapten-induced colitis is associated with colonic patch hypertrophy and T helper cell 2-type responses. J Exp Med 1999 189 : 1169 80.
27. Wallace JL, McKnight W, Asfaha S, Liu DY. Reduction of acute and reactivated colitis in rats by an inhibitor of neutrophil activation. Am J Physiol 1998 274 : G802 8.
28. Dieleman LA, Elson CO, Tennyson GS, Beagley KW. Kinetics of cytokine expression during healing of acute colitis in mice. Am J Physiol 1996 271 : G130 6.
29. Ameho CK, Adjei AA, Harrison EK et al. Prophylactic effect of dietary glutamine supplementation on interleukin 8 and tumour necrosis factor alpha production in trinitrobenzene sulphonic acid induced colitis. Gut 1997 41 : 487 93.
30. Freeman GJ, Gribben JG, Boussiotis VA et al. Cloning of B7-2: a CTLA-4 counter-receptor that costimulates human T cell proliferation. Science 1993 262 : 909 11.
31. Hathcock KS, Laszlo G, Pucillo C, Linsley P, Hodes RJ. Comparative analysis of B7-1 and B7-2 costimulatory ligands: expression and function. J Exp Med 1994 180 : 631 40.
32. Elson CO, Beagley KW, Sharmanov AT et al. Hapten-induced model of murine inflammatory bowel disease: mucosa immune responses and protection by tolerance. J Immunol 1996 157 : 2174 85.
33. Wood PA, Amendt BA, Rhead WJ, Millington DS, Inoue F, Armstrong D. Short-chain acyl-coenzyme A dehydrogenase deficiency in mice. Pediatr Res 1989 25 : 38 43.
34. Fiocchi C. Lymphokines and the intestinal immune response. Role in inflammatory bowel disease. Immunol Invest 1989 18 : 91 102.
35. Neurath MF, Fuss I, Kelsall BL, Stuber E, Strober W. Antibodies to interleukin 12 abrogate established experimental colitis in mice. J Exp Med 1995 182 : 1281 90.
36. Santucci L, Agostini M, Bruscoli S et al. GITR modulates innate and adaptive mucosal immunity during the development of experimental colitis in mice. Gut 2007 56 : 52 60.
37. Sheibanie AF, Yen JH, Khayrullina T et al. The proinflammatory effect of prostaglandin E2 in experimental inflammatory bowel disease is mediated through the IL-23-> IL-17 axis. J Immunol 2007 178 : 8138 47.
38. D'Odorico A, Bortolan S, Cardin R et al. Reduced plasma antioxidant concentrations and increased oxidative DNA damage in inflammatory bowel disease. Scand J Gastroenterol 2001 36 : 1289 94.
39. D'Argenio G, Cosenza V, Delle Cave M et al. Butyrate enemas in experimental colitis and protection against large bowel cancer in a rat model. Gastroenterology 1996 110 : 1727 34.
40. Frenkel K. Carcinogen-mediated oxidant formation and oxidative DNA damage. Pharmacol Ther 1992 53 : 127 66.
41. Halliwell B, Gutteridge JM. Lipid peroxidation, oxygen radicals, cell damage, and antioxidant therapy. Lancet 1984 1 : 1396 7.
42. Wang C, Sadovova N, Ali HK et al. L-carnitine protects neurons from 1-methyl-4-phenylpyridinium-induced neuronal apoptosis in rat forebrain culture. Neuroscience 2007 144 : 46 55.
43. Rauchova H, Koudelova J, Drahota Z, Mourek J. Hypoxia-induced lipid peroxidation in rat brain and protective effect of carnitine and phosphocreatine. Neurochem Res 2002 27 : 899 904.
44. Gulcin I. Antioxidant and antiradical activities of L-carnitine. Life Sci 2006 78 : 803 11.