Role of phospholipase A2 and tyrosine kinase in Clostridium difficile toxin A-induced disruption of epithelial integrity, histologic inflammatory damage and intestinal secretion

Journal of Applied Toxicology

Volumn 28, Issue 7, 2008, Pages 849-857

  Lima, Aldo A M ^a,b   Nascimento, Nilberto R F ^c   Fang, Guodong D ^a   Yotseff, Peter ^a   Toyama, M H ^d   Guerrant, Richard L ^a,b   Fonteles, Manassés C ^a,b,e,f  

^a UNIVERSITY OF VIRGINIA   (United States)

^b FEDERAL UNIVERSITY OF CEARÁ   (Brazil)

^c STATE UNIVERSITY OF CEARÁ   (Brazil)

^d SÃO PAULO STATE UNIVERSITY UNESP   (Brazil)

^e MACKENZIE PRESBYTERIAN UNIVERSITY   (Brazil)

^f NONE   (Brazil)

Author keywords

C. difficile; Cytoskeleton disruption; Diarrhea; Erbstatin; F actin; GTPases; PLA2; PLA2 inhibitors; Tight junctions; Toxin A enterotoxin

Indexed keywords

4 BROMOPHENACYL BROMIDE; ARISTOLOCHIC ACID; CLOSTRIDIUM DIFFICILE TOXIN A; ERBSTATIN; F ACTIN; INDOMETACIN; MEPACRINE; NORDIHYDROGUAIARETIC ACID; PHOSPHOLIPASE A2; PROTEIN TYROSINE KINASE; BACTERIAL TOXIN; ENTEROTOXIN; ENZYME INHIBITOR; TCDA PROTEIN, CLOSTRIDIUM DIFFICILE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; DRUG EFFECT; ENZYME INHIBITION; EXPERIMENTAL RABBIT; HISTOPATHOLOGY; ILEUM; INFLAMMATION; INTESTINAL BLEEDING; INTESTINE EPITHELIUM; INTESTINE SECRETION; MALE; NONHUMAN; PRIORITY JOURNAL; PROTEIN FUNCTION; TIGHT JUNCTION; ANIMAL; DISEASE MODEL; DRUG ANTAGONISM; DRUG COMBINATION; INTESTINE MUCOSA; PATHOLOGY; PHYSIOLOGY; RABBIT; SECRETION; TUMOR CELL LINE;

CLOSTRIDIUM DIFFICILE; ORYCTOLAGUS CUNICULUS;

ANIMALS; BACTERIAL TOXINS; CELL LINE, TUMOR; DISEASE MODELS, ANIMAL; DRUG COMBINATIONS; ENTEROTOXINS; ENZYME INHIBITORS; ILEUM; INDOMETHACIN; INTESTINAL MUCOSA; MALE; PHOSPHOLIPASES A2; PROTEIN-TYROSINE KINASES; QUINACRINE; RABBITS;

EID: 55449095667     PISSN: 0260437X     EISSN: 10991263     Source Type: Journal    
DOI: 10.1002/jat.1348     Document Type: Article

References (37)

1. Adams RB, Guerrant RL, Zu S, Fang G, Roche JK. 1994. Cryptosporidium parvum infection of intestinal epithelium: morphologic and functional studies in an in vitro model. J. Infect. Dis. 169: 170-177.
2. Alcantara C, Stenson WF, Steiner TS, Guerrant RL. 2001. Role of inducible cyclooxygenase and prostaglandins in Clostridium difficile toxin A-induced secretion and inflammation in an animal model. J. Infect. Dis. 184: 648-652.
3. Alcantara CS, Jin XH, Brito GA, Carneiro-Filho BA, Barrett LJ, Carey RM, Guerrant RL. 2005. Angiotensin II subtype 1 receptor blockade inhibits Clostridium difficile toxin A-induced intestinal secretion in a rabbit model. J. Infect. Dis. 191: 2090-2096.
4. Archibald LK, Banerjee SN, Jarvis WR. 2004. Secular trends in hospital-acquired Clostridium difficile disease in the United States, 1987-2001. J. Infect. Dis. 189: 1585-1589.
5. Aslam S, Hamill RJ, Musher DM. 2005. Treatment of Clostridium difficile-associated disease: old therapies and new strategies. Lancet Infect. Dis. 5: 549-557.
6. Baldacini O, Girardot R, Green GA, Rihn B, Monteil H. 1992. Comparative study of immunological properties and cytotoxic effects of Clostridium difficile toxin B and Clostridium sordellii toxin L. Toxicon 30: 129-140.
7. Banno Y, Kobayashi T, Kono H, Watanabe K, Veno K, Nozawa Y. 1984. Biochemical characterization and biologic actions of two toxins (D-1 and D-2) from Clostridium difficile. Rev. Infect. Dis. 6: S11-S20.
8. Brito GA, Fujji J, Carneiro-Filho BA, Lima AA, Obrig T, Guerrant RL. 2002. Mechanism of Clostridium difficile toxin A-induced apoptosis in T84 cells. J. Infect. Dis. 186(10): 1438-1447.
9. Carneiro BA, Fujii J, Brito GA, Alcantara C, Oria RB, Lima AA, Obrig T, Guerrant RL. 2006. Caspase and Bid Involvement in Clostridium difficile toxin A-induced apoptosis and modulation of toxin a effects by glutamine and alanyl-glutamine in vivo and in vitro. Infect. Immun. 74: 81-87.
10. Cereijido M, Meza I, Martinez-Palomo A. 1981. Occluding junctions in cultured epithelial monolayers. Am. J. Physiol. 240: C96-C102.
11. Coso OA, Chiariello M, Yu JC, Teramoto H, Crespo P, Xu N, Miki T, Gutkind JS. 1995. The small GTP-binding proteins Rac1 and Cdc42 regulate the activity of the JNK/SAPK signaling pathway. Cell 81(7): 1137-1146.
12. Dharmsathaphorn K, McRoberts JA, Mandel KG, Tisdale LD, Masui H. 1984. A human colonic tumor cell line that maintains vectorial electrolyte transport. Am. J. Physiol. 246: G204-G208.
13. Fonteles M, Fang G, Thielman NM, Yotseff PS, Guerrant RL. 1995. Role of platelet activating factor in the inflammatory and secretory effects of Clostridium difficile toxin A. J. Lipid Mediat. Cell Signal. 11: 133-143.
14. Gerhard R, Tatge H, Genth H, Thum T, Borlak J, Fritz G, Just I. 2005. Clostridium difficile toxin A induces expression of the stress-induced early gene product RhoB. J. Biol. Chem. 280(2): 1499-505.
15. Hecht G, Pothoulakis C, LaMont JT, Madam JL. 1988. Clostridium difficile toxin A perturbs cytoskeletal structure and tight junction permeability of cultured human intestinal epithelial monolayers. J. Clin. Invest. 82: 1516-1524.
16. Ishida Y, Maegawa T, Kondo T, Kimura A, Iwakura Y, Nakamura S, Mukaida N. 2004. Essential involvement of IFN-gamma in Clostridium difficile toxin A-induced enteritis. J. Immunol. 172: 3018-3025.
17. Kim H, Rhee SH, Kokkotou E, Na X, Savidge T, Moyer MP, Pothoulakis C, LaMont JT. 2005. Clostridium difficile toxin A regulates inducible cyclooxygenase-2 and prostaglandin E2 synthesis in colonocytes via reactive oxygen species and activation of p38 MAPK. J. Biol. Chem. 280(22): 21237-21245.
18. Lamarche N, Tapon N, Stowers L, Burbelo PD, Aspenstrom P, Bridges T, Chant J, Hall A. 1996. Rac and Cdc42 induce actin polymerization and G1 cell cycle progression independently of p65PAK and the JNK/SAPK MAP kinase cascade. Cell 87(3): 519-529.
19. Lima AAM, Lyerly DM, Wilkins TD, Innes DJ, Guerrant RL. 1988. Effects of Clostridium difficile toxins A and B in rabbit small and large intestine in vivo and on cultured cells in vitro. Infect. Immun. 56: 582-588.
20. Lima AAM, Innes DJ, Chadee K, Lyerly DM, Wilkins TD, Guerrant RL. 1989. Clostridium difficile toxin A: interactions with mucus and early sequential histopathologic effects in rabbit small intestine. Lab. Invest. 61: 419-425.
21. Madara JL, Stafford J, Dharmsathaphom K, Carlson S. 1987. Structural analysis of a human intestinal epithelial cell line. Gastroenterology 92: 1131-1145.
22. Matter K, Balda MS. 2003. Functional analysis of tight junctions. Methods 30(3): 228-234.
23. McClane BA. 2001. The complex interactions between Clostridium perfringens enterotoxin and epithelial tight junctions. Toxicon 39(11): 1781-1791.
24. McDonald LC, Killgore GE, Thompson A, Owens RC Jr, Kazakova SV, Sambol SP, Johnson S, Gerding DN. 2005. An epidemic, toxin gene-variant strain of Clostridium difficile. New Engl. J. Med. 353: 2433-2441.
25. McVey DC, Vigna SR. 2005. The role of leukotriene B4 in Clostridium difficile toxin A-induced ileitis in rats. Gastroenterology 128: 1306-1316.
26. Minden A, Lin A, Claret FX, Abo A, Karin M. 1995. Selective activation of the JNK signaling cascade and c-Jun transcriptional activity by the small GTPases Rac and Cdc42Hs. Cell 81(7): 1147-1157.
27. National Research Council. 1997. Occupational Health and Safety in the Care and Use of Research Animals. National Academy Press: Washington, DC.
28. Pépin J, Valiquette L, Cossette B. 2005. Mortality attributable to nosocomial Clostridium difficile-associated disease during an epidemic caused by a hypervirulent strain in Quebec. Can. Med. Assoc. J. 173: 1037-1042.
29. Pothoulakis C, Sullivan R, Malnick DA, Triadafilopoulos G, Gadenne AS, Meshulam T, LaMont JT. 1988. Clostridium difficile toxin A stimulates intracellular calcium release and chemotactic response in human granulocytes. J. Clin. Invest. 81(6): 1741-1745.
30. Powell DW. 1992. Epithelial secretory responses to inflammation. Platelet activating factor and reactive oxygen metabolites. Ann. NY Acad. Sci. 664: 232-247.
31. Reynolds LJ, Hughes LL, Dennis EA. 1992. Analysis of human synovial fluid phospholipase A2 on short chain phosphatidylcholine-mixed micelles: development of a spectrophotometric assay suitable for a microtiterplate reader. Anal Biochem. 204(1): 190-197.
32. Rocha MF, Soares AM, Flores CA, Steiner TS, Lyerly DM, Guerrant RL, Ribeiro RA, Lima AA. 1998. Intestinal secretory factor released by macrophages stimulated with Clostridium difficile toxin A: role of interleukin 1beta. Infect. Immun. 66: 4910-4916.
33. Toyama MH, de Oliveira DG, Beriam LOS, Novello JC, Rodrigues-Simioni L, Marangoni S. 2003. Structural, enzymatic and biological properties of new PLA(2) isoform from Crotalus durissus terrificus venom. Toxicon 41(8): 1033-1038.
34. Van Itallie CM, Anderson JM. 2004. The molecular physiology of tight junction pores. Physiology (Bethesda) 19: 331-338.
35. Van Itallie CM, Fanning AS, Anderson JM. 2003. Reversal of charge selectivity in cation or anion-selective epithelial lines by expression of different claudins. Am. J. Physiol. Renal Physiol. 285(6): F1078-1084.
36. Warny M, Pepin J, Fang A, Killgore G, Thompson A, Brazier J, Frost E, McDonald LC. 2005. Toxin production by an emerging strain of Clostridium difficile associated with outbreaks of severe disease in North America and Europe. Lancet 366: 1079-1084.
37. Wen-Hwa L, Toyama MH, Soares AM, Giglio JR, Marangoni S, Polikarpov I. 1999. Crystallization and preliminary X-ray diffraction studies of piratoxin III, a D-49 phospholipase A(2) from the venom of Bothrops pirajai. Acta Crystallogr. D Biol. Crystallogr. 55: 1229-1230.