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Diarrhée et cascade inflammatoire: une nouvelle approche

Inflammatory cascade and diarrhoea: a new approach

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Acta Endoscopica

Résumé

Les maladies diarrhéiques, responsables d’une forte morbidité et mortalité à travers le monde sont le plus souvent induites par l’infection microbienne. Les microorganismes (bactéries, virus, parasites) en interagissant avec les cellules épithéliales de l’hôte, induisent une cascade inflammatoire.

L’approche physiologique de l’étiologie des diarrhées aiguës démontre l’importance des mécanismes de l’inflammation dans les désordres de la muqueuse intestinale. Les interactions des pathogènes avec les cellules épithéliales induisent l’activation de facteurs transcriptionnels tels que NF kappa B, les MAP kinases, liés à la production de cytokines.

Parallèlement, l’infection microbienne provoque la libération de radicaux libres oxygénés. Parmi ces radicaux, de fortes productions de monoxyde d’azote (NO) peuvent générer en présence d’anion superoxyde le radical peroxynitrite, connu pour ses effets délétères sur les tissus.

Finalement, plus tardivement, l’apoptose induite par les cytokines pro-inflammatoires peut servir à éliminer les cellules immunitaires ou à évacuer les défenses de l’hôte pour limiter l’infection.

Comme la barrière intestinale n’est pas une barrière inerte, les mécanismes de défense de la muqueuse réagissent contre l’agression de type inflammatoire. Après l’infection microbienne, la mucine extracellulaire est augmentée pour réduire l’adhérence des microorganismes. Mais l’effet le plus important est observé au niveau des jonctions étroites qui contrôlent et maintiennent la résistance transépithéliale et les flux de molécules par voie paracellulaire.

En conclusion, le processus inflammatoire initialisé par l’infection microbienne entraîne des diarrhées aiguës. Comme dans certains cas, la diarrhée est persistante avec une inflammation chronique, il y a un risque de développer le syndrome de l’intestin irritable. Pour protéger la muqueuse intestinale contre les conséquences sévères de l’inflammation, il est nécessaire de prévenir l’interaction des pathogènes avec les cellules épithéliales en augmentant les défenses de la barrière muqueuse.

Summary

Diarrheal diseases, actually recognized for high morbidity and mortality in the world, most commonly are induced by microbial infection. The microorganisms (bacteria, viruses, parasites), by an interaction with the intestinal epithelial cells of the host, induce an inflammatory cascade. Physiological approach of the etiology of the acute diarrhea, demonstrates the importance of the mechanisms of inflammation in the disorders of the intestinal mucosa. Pathogen interactions with the epithelial cells induce activation of transcriptional factors such as NF kappa B, Map kinases linked to the production of cytokines. Parallely, microbial infection provokes the release of oxygenated free radicals. Among these radicals, high production of nitric oxide (NO) can generate, in the presence of Superoxide anion, the peroxinitrite radical known for its deleterious effects on the host tissues. Finally, in a relatively late event, apoptosis induced by the proinflammatory cytokines may serve to eliminate immune cells or evacuate host defences for limiting infection.

As the intestinal barrier is not a static barrier, mucosal defence mechanisms react against inflammatory pathogen aggression. After microbial infection, extracellular mucin is increased to reduce the microorganism adherence. But, the major effect is observed on the tight junction barrier that controls and maintains the transepithelial resistance and the paracellular flux of macromolecules.

In conclusion, inflammatory process initialised by microbial infection causes acute diarrhea. As in certains cases the diarrhea is persistent with chronic inflammation, there is a risk to develop irritable bowel syndrome. To protect the intestinal mucosa against severe inflammation consequences, it is necessary to prevent pathogen interaction with the epithelial cells by increasing the mucosa barrier defences.

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Références

  1. EAVES-PYLES T, SZABO C., SALZMAN AL. Bacterial invasion is not required for activation of NF-Kappa B in enterocytes.Infect Immun 1999; 67: 800–4.

    PubMed  CAS  Google Scholar 

  2. GUERRANT RL. Lessons from diarrheal diseases: demography molecular pharmacology.J Infect Dis 1994; 169 (6): 1206–18.

    PubMed  CAS  Google Scholar 

  3. GUERRANT RL, STEINER TS, LIMA AA, BOBAK DA. How intestinal bacteria cause disease.J Infect Dis 1999; 179 (suppl 2): S 331-S 7.

    Article  Google Scholar 

  4. FARTHING MJ. Novel targets for the pharmacotherapy of diarrhea: a view for the millenium.J Gastroenterol Hepatol 2000; 15: G38-G45.

    Article  PubMed  Google Scholar 

  5. STEPHEN J. Pathogenesis of infectious diarrhea.Can J Gastroenterol 2001; 10: 669–83.

    Google Scholar 

  6. SUAREZ J, SALAMONE FR. Management and prevention of bacterial diarrhea.Clin Pharm 1988; 7(10): 746–59.

    PubMed  CAS  Google Scholar 

  7. ZIJLSTRA RT, MCCRACKEN BA, ODLE J, DONOVAN SM, GELBERG HB, PETSCHOW B, ZUCKERMAN FA, GASKINS HR. Malnutrition modifies pig small intestinal responses to rotavirus.J Nutr 1999; 129: 838–43.

    PubMed  CAS  Google Scholar 

  8. SANSONETTI PJ, TRAN Van Nhieu G., EGILE C. Rupture of the intestinal epithelial barrier and mucosal invasion byShigella flexneri.Clin Infect Dis 1999; 28 (3): 466–75.

    Article  PubMed  CAS  Google Scholar 

  9. NEAL KR, HEBDEN J, SPILLER R. Prevalence of gastrointestinal symptoms six months after bacterial gastroenteritis and risk factors for development of the irritable bowel syndrome: postal survey of patients.BMJ 1997; 314 (7083): 779–82.

    PubMed  CAS  Google Scholar 

  10. PIMENTEL M, CHOW EJ, LIN HC. Eradication of small intestinal overgrowth reduces symptoms of irritable bowel syndrome.Am J Gastroenterol 2000; 95 (12): 3503–6.

    Article  PubMed  CAS  Google Scholar 

  11. AZIM T, ISLAM LN, SARKER MS, AHMAD SM, HAMODANI JD, FARUUQUE SM, SALAM MA. Immune response of Bengladeshi children with acute diarrhea who subsequently have persistent diarrhea.J Pediatr Gastroenterol Nutr 2000; 31 (5): 528–35.

    Article  PubMed  CAS  Google Scholar 

  12. HAUSSMAN M, KIESSLING S, MESTERMANN S, WEBB C., SPOTTL T, ANDUS T, SCHOLMERICH J, HERFARTH H, RAY F, FALK W, ROGLER G. Toll-like receptors 2 and 4 are up-regulated during intestinal inflammation.Gastroenterology 2002; 122 (7): 1987–2000.

    Article  CAS  Google Scholar 

  13. HERSHBERG RM. The epithelial cell cytoskeleton and intracellular trafficking. Polarized compartmentalization of antigen processing and Toll-like receptor signaling in intestinal epithelial cells.Am J Physiol Gastrointest Liver Physiol 2002; 283 (4): G833–9.

    PubMed  CAS  Google Scholar 

  14. GEWIRTZ AT. Intestinal epithelial Toll-like receptors: to protect and serve ?Curr Pharm Des 2003; 9 (1): 1–5.

    Article  PubMed  CAS  Google Scholar 

  15. CHAMAILLARD M, GIRARDIN SE, VIALA J, PHILPOTT DJ. Nods, Nalps and Naip: intracellular regulators of bacterial-induced inflammation.Cell Microbiol 2003; 5 (9): 581–92.

    Article  PubMed  CAS  Google Scholar 

  16. ELEWAUT D, DIDONATO JA, MOGG Kim J., TRUONG F, ECKMANN L, KAGNOFF MF. NF kappa B is a central regulator of the intestinal epithelial cell innate immune response induced by infection with enteroinvasive bacteria.J Immunol 1999; 163:1457–66.

    PubMed  CAS  Google Scholar 

  17. BAUERLE PA, HENKEL T. Function and activation of NF kappa B in the immune system.Ann Rev Physiol 1994; 12:141–79.

    Google Scholar 

  18. BERKES J., VISWANATHAN VK, SAVKOVIC SD, HECHT G. Intestinal epithelial responses to enteric pathogens: effects on the tight junction barrier, ion transport and inflammation.Gut 2002; 52:439–51.

    Article  Google Scholar 

  19. STABEL S, PARKER PJ. Protein Kinase C..Pharmacol Ther 1991; 51:71–95.

    Article  PubMed  CAS  Google Scholar 

  20. KIM JML, ECKMAN TC, SAVIDGE DC, LOWE T, WITTHOFT T, KAGNOFF MF. Apoptosis of human intestinal epithelial cells after bacterial invasion.J Clin Invest 1998; 102:1815–21.

    Article  PubMed  CAS  Google Scholar 

  21. MAHIDA YR, MAKH S, HYDE S, GRAY T, BORRIELLO SP. Effect ofClostridium difficile toxin A on human epithelial cells: induction of interleukin 8 production and apoptosis after cell detachment.Gut 1996; 38 (3): 337–47.

    Article  PubMed  CAS  Google Scholar 

  22. CRANE JK, OH JS. Activation of host cell protein kinase C by enteropathogenicEscherichia coli.Infect Immun 1997; 65: 3277–85.

    PubMed  CAS  Google Scholar 

  23. SAVKOVIC S, KOUTSOURIS A, HECHT G. Activation of NF kappa B in intestinal epithelial cells by enteropathogenicEscherichia coli.Am J Physiol 1997; 273: C1160–7.

    PubMed  CAS  Google Scholar 

  24. JEFFERSON KK, SMITH MF, BOBAK DA. Role of intracellular calcium and NF kappa B in theClostridium difficile toxin A induced up-regulation and secretion of 11-8 from human monocytes.J Immunol 1999; 60: 237–48.

    Google Scholar 

  25. GEWIRTZ AT, SIMON PO, SCHMITT CK, TAYLOR LJ, HAGEDOM CH, O’BRIEN Adn Neish AS, MADARA JL.Salmonella typhimurium translocates flagellin across intestinal epithelia, inducing a pro inflammatory response.J Clin Invest 2001; 107 (1): 99–109.

    Article  PubMed  CAS  Google Scholar 

  26. GALDIERO M, VITIELLO, M, SANZARI E, DTSANTO M, TORTORA A, LONGANELLA A, GALDIERO S. Porins fromSalmonella entérica serovar Typhimirium activate the transcription factors activating protein 1 and NF-kappa B through the Raf-1 mitogen-activated protein kinase cascade.Infect Immun 2002; 70 (2): 558–68.

    Article  PubMed  CAS  Google Scholar 

  27. KAYAL S, BERCHE P. L’activation du NF Kappa B au cours des infections bactériennes: une réaction primordiale de défense de l’hôte.Hépato-Gastro 2000; 7 (3): 199–209.

    Google Scholar 

  28. AKHTAR M, WATSON JL, NAZLI A, MCKAY DM. Bacterial DNA evokes epithelial IL-8 production by a MAPK-dependent, NFKappa B-independent pathway.FASEB J. 2003; 17 (10): 1319–21.

    PubMed  CAS  Google Scholar 

  29. SCHREIBER S. Maladies inflammatoires chroniques de l’intestin et immunité.Hépato-Gastro 1999; 6 (hors série): 1–11.

    Google Scholar 

  30. MADARA JL, STAFFORD J. Interferon gamma directly affects barrier function of cultured intestinal epithelial monolayers.J Clin Invest 1989; 83:724–8.

    Article  PubMed  CAS  Google Scholar 

  31. DEEM RL, SHANAHAN F, TARGAN SR. Trigerred human mucosal T cells release Tumor Necrosis Factor alpha and Interferon gamma which kill human colonic epithelial cells.Clin Exp Immunol 1991; 83:79–81.

    PubMed  CAS  Google Scholar 

  32. ROLLO EE, PRASANNA Kumar K., REICH NC, COHEN J, ANGEL J, GREENBERG HB, SHETH R, ANDERSON J, OH B, HEMPSON SJ, MACKOW ER, SHAW RD. The epithelial cell response to rotavirus infection.J Immunol 1999; 163: 4442–52.

    PubMed  CAS  Google Scholar 

  33. ROCHA MF, SIDRIM JJ, LIMA AA.Clostridium difficile as an inducer of inflammatory diarrhea.Rev Soc Bras Med Trop 1999; 32 (1): 47–52.

    Article  PubMed  CAS  Google Scholar 

  34. GIANELLA RA. Pathogenesis of acute bacterial diarrheal disorders.Ann Rev Med 1981; 32: 341–57.

    Article  Google Scholar 

  35. ISLAM D, VERESS B, BARDHAN PK, LINDBERG A, CHRISTENSSON B. In situ characterisation of inflammatory responses in the rectal mucosae of patients with Shigellosis.Infect Immun 1997; 65:739–49.

    PubMed  CAS  Google Scholar 

  36. KIRKPATRICK BD, DANIELS MM, JEAN SS, PAPE JW, LITTENBERG B, FITZGERALD DW, LEDERMAN HM, NATARO JP, SEARS CL. Cryptosporidiosis stimulates an inflammatory intestinal response in malnourished Haitian Children.J Infect Dis 2002; 186 (1): 94–100.

    Article  PubMed  Google Scholar 

  37. SEYDEL KB, LI E, SWANSON PE, STANNEY SL. Human intestinal epithelial cells produce proinflammatory cytokines in response to infection in a SCID mouse human intestinal xenograft model of amibiasis.Infect Immun 1997; 6 (5): 1631–9.

    Google Scholar 

  38. COLLINS SM. Irritable Bowel syndrome could be an inflammatory disorder.Eur J Gastrol Hepatol 1994; 6: 478–83.

    Article  Google Scholar 

  39. BOVERIS A. Biochemistry of free radicals: from electrons to tissues.Medicina (B. Aires) 1998; 58 (4): 350–6.

    CAS  Google Scholar 

  40. MACDONALD TT, MURCH SH, NICHOLLS SW, BREESE EJ. Diarrheal disease: current concepts and future challenges. Intestinal cytokines in inflammatory bowel disease and invasive diarrhea.Trans R Soc Trop Med 1993; 87 (suppl 3): 23–6.

    Article  Google Scholar 

  41. SODHI CP, KATYAL R, RANA SV, ATTRI S, SINGH V. Study of oxidative stress in rotavirus infected infant mice.Indian J Med Res 1996; 104:245–9.

    PubMed  CAS  Google Scholar 

  42. CHIUA M, GUARNER C, PERALTA Cl, LOVET T, GOMEZ G, SORIANO G, BALENZO J. Intestinal mucosa damage and bacterial translocation in cirrhotic rats.Eur J Gastroenterol Hepatol 2003; 15 (2): 145–50.

    Article  Google Scholar 

  43. IZZO AA, MASCOLO N, CAPASSO F. Nitric oxide as a modulator of intestinal water and electrolyte transport.Dig Dis Sci 1998; 43 (8): 1605–20.

    Article  PubMed  CAS  Google Scholar 

  44. WITTHÖFT T, ECKMANN L, KIM JM, KAGNOFF MF. Enteroinvasive bacteria directly activate expression of iNOS and NO production in human colon epithelial cells.Am J Physiol 1998; 275 (3 Pt 1): G564-G71.

    PubMed  Google Scholar 

  45. NATHAN C. Inductible nitric oxide synthase. What difference does it make ?J Clin Invest 1007; 100: 2417–23.

    Article  Google Scholar 

  46. SALZMAN AL, MENCONI MJ, UNNO N, EZZELL RM, CASEYZ DM, GONZALEZ PK, FINK MP. Nitric oxide dilates tight junctions and deplets ATP in cultures Caco-2 Bbe intestinal epithelial monolayers.Am J Physiol 1995; 368 (Gastrointest Liver Physiol 31): G361-G73.

    Google Scholar 

  47. Kubes P, MacCafferty DM. Nitric oxide and intestinal inflammation.Am J Med 2000; 109.

  48. TEPPERMAN BL, BROWN JF, KOROLKIEWICZ R, WHITTLE BJ. Nitric oxide synthase activity, viability and cyclic GMP levels in rat colonie epithelial cells: effect of endotoxin challenge.J Pharmacol Exp Ther 1994; 271: 1477–82.

    PubMed  CAS  Google Scholar 

  49. WRIGHT NA, IRWIN M. The kinetics of villus cell population in the mouse small intestine. 1. Normal villi: the steady state requirement.Cell Tissue 1982; 15: 595–609.

    CAS  Google Scholar 

  50. MOGG Kim J., ECKMANN L, SAVIDGE TC, LOWE DC, WITHÖFT T, KAGNOTT MF. Apoptosis of human intestinal epithelial cells after bacterial invasion.J Clin Invest 1998; 102: 1815–23.

    Article  Google Scholar 

  51. WEINRAUCH Y, ZYCHLINSKY A. The induction of apoptosis by bacterial pathogens.Ann Rev Microbiol 1999; 53:155–87.

    Article  CAS  Google Scholar 

  52. KAGNOFF MF, ECKMANN L. Epithelial cells as sensors for microbial infection.J Clin Invest 1997; 100: 6–10.

    Article  PubMed  CAS  Google Scholar 

  53. GRELL MG, ZIMMERMANN D, HULSER K, PLIZENMMAIER K, SCHEURICH P. TNF receptors TR60 and TR80 mediate apoptosis via induction of distinct signal pathways.J Immunol 1994; 153: 1963–72.

    PubMed  CAS  Google Scholar 

  54. ABRIEU-MARTIN MT, VIDRICH A, LYNCH DH, TARGAN SR. Divergent induction of apoptosis and Il-8 secretion in HT 29 cells in response to TNF alpha and ligation of FAS antigen.J Immunol 1995; 155:4147–54.

    Google Scholar 

  55. ECKMANN L, KAGNOFF MF, FIERER J. Epithelial cells secrete the chemokine interleukine 8 in response to bacterial entry.Inf Immun 1993; 61 (11): 4569–74.

    CAS  Google Scholar 

  56. JUNG HC, ECKMANN L, YANG SK, PANJA A, FIERER J, MORZYCKA-WROBLEWSKA E, KAGNOFF MF. A distinct array of proinflammatory cytokines is expressed in human colon epithelial cells in response to bacterial invasion.J Clin Invest 1995; 95: 55–65.

    Article  PubMed  CAS  Google Scholar 

  57. DECLAN F, COLE MC, ECKMANN L, LAURENT F, KAGNOFF MF. Intestinal epithelial cell apoptosis followingCryptosporidium parvum infection.Infect Immun 2000; 68 (3): 1710–3.

    Article  Google Scholar 

  58. NUTTEN S, SANSONETTI P, HUET G, BOURDON-BISIAUX C., MERESSE B, COLOMBEL JF, DESREUMAUX P. Epithelial inflammation response induced byshigella flexneri depends on mucin gene expression.Microbes Infect 2002; 4 (11): 1121–4.

    Article  PubMed  CAS  Google Scholar 

  59. HECHT G. Microbes and microbial toxins: paradigms for microbial-mucosal interactions. VII: EnteropathogenicEscherichia coli: physiological alterations from an extracellular position.Am J Physiol Gastroenterol Liver Physiol 2001; 281 (1): G1-G7.

    CAS  Google Scholar 

  60. JUST I, FRITZ G, AKTORIES K, GIRY M, POPOFF MR, BOQIET P, HEGENBARTH S, von EICHEL-STREIBER C.Clostridium difficile toxin B acts on the GTP-binding protein Rho.J Biol Chem 1994; 269 (14): 10706–12.

    PubMed  CAS  Google Scholar 

  61. HECHT G, POTHOULAKIS C., LAMONT JT, MADARA JL.Clostridium difficile toxin A perturbs cytoskeletal srtucture and tight junction permeability of cultured human intestinal monolayers.Clin Invest 1988; 82 (5): 1516–24.

    Article  CAS  Google Scholar 

  62. CHEN M, POTHOULAKIS C., LAMONT J. Protein kinase C signaling regulates ZO-1 translocation and increased parcellular flux of T84 colonocytes exposed toClostridium difficile Toxin A..J Biol Chem 2002; 277: 4247–54.

    Article  PubMed  CAS  Google Scholar 

  63. KNUTTON S, LLOYD D, MCNEISH A. Adhesion of EnteropathogenicEscherichia coli to human intestinal epithelial monolayers diminishes barrier function.Am J Physiol 1995; 268: G374-G9.

    Google Scholar 

  64. FARSHORI P, KACHAR B. Redistribution and phosphorylation of occluding during opening and releasing of tight junctions in cultures epithelial cells.J Membran Biol 1999; 170:147–56.

    Article  CAS  Google Scholar 

  65. WU S, LIM K, HUANG J, SAIDI RF, SEARS CL.Bacteroides fragilis enterotoxin claeves the zonula adherens protein E-Cadherin.Proc Natl Acad Sci USA 1998; 95 (25): 14979–84.

    Article  PubMed  CAS  Google Scholar 

  66. MCCLANS B.Costridium perfringens enterotoxin acts by producing small molecule permeability alterations in plasma membranes.Toxicology 1994; 87: 43–67.

    Article  Google Scholar 

  67. Van ELBURG RM, UIL JJ, deMONCHY JG, HEYMANS H. Intestinal permeability in pédiatrie gastroenterology.Scand I Gastroenterol 1992; 194 (Suppl): 19–24.

    Article  Google Scholar 

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  1. Laboratoires d’Etudes Biologiques, 8, rue Auguste Salluel, 60370, Hermes, France

    Marie-Thérèse Droy-Lefaix

  2. Unité de Neuro-Gastroentérologie & Nutrition, Toulouse, France

    L. Bueno

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  1. Marie-Thérèse Droy-Lefaix
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Droy-Lefaix, MT., Bueno, L. Diarrhée et cascade inflammatoire: une nouvelle approche. Acta Endosc 33, 773–780 (2003). https://doi.org/10.1007/BF03002623

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