Analysis of Inflammatory Cytokines from the Cecum and Proximal Colon of Mice Infected with Enterotoxigenic Bacteroides fragilis

  • Hwang, Soonjae (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University at Wonju) ;
  • Lee, Min Ho (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University at Wonju) ;
  • Gwon, Sun-Yeong (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University at Wonju) ;
  • Lee, Seunghyung (Department of Anatomy & Cell Biology, Temple University School of Medicine) ;
  • Jung, Dongju (Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University) ;
  • Rhee, Ki-Jong (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University at Wonju)
  • Received : 2013.05.14
  • Accepted : 2013.06.22
  • Published : 2013.06.29

Abstract

Enterotoxigenic Bacteroides fragilis (ETBF) causes inflammatory diarrhea in humans and animals and is also implicated in colorectal cancer. ETBF-infected mice exhibit a prominent large intestinal inflammation characterized by neutrophil infiltration and induction of the Th17 response. In this study, we examined differences in the secreted cytokine profile of the cecum and proximal colon of ETBF-infected mice using an antibody array. Of the cytokines examined, we found that the cecal tissues from ETBF-infected mice secreted elevated levels of G-CSF, IL-6, IL-17 and LIX compared to non-toxigenic Bacteroides fragilis (NTBF) and Mock infected mice. The proximal colon tissues from ETBF-infected mice secreted higher levels of G-CSF, IL-6, KC, LIX, MIP-1g and MCP-1. This study demonstrates that the cecum and colon should be considered separately when assays are used to determine immune responsiveness to enteric infections.

Keywords

References

  1. Franco AA, Mundy LM, Trucksis M, Wu S, Kaper JB, Sears CL. Cloning and characterization of the Bacteroides fragilis metalloprotease toxin gene. Infect Immun. 1997. 65: 1007-1013.
  2. Goodwin AC, Destefano Shields CE, Wu S, Huso DL, Wu X, Murray-Stewart TR, Hacker-Prietz A, Rabizadeh S, Woster PM, Sears CL, Casero RA, Jr. Polyamine catabolism contributes to enterotoxigenic Bacteroides fragilis-induced colon tumorigenesis. Proc Natl Acad Sci U S A. 2011. 108: 15354-15359. https://doi.org/10.1073/pnas.1010203108
  3. Moncrief JS, Obiso R, Jr., Barroso LA, Kling JJ, Wright RL, Van Tassell RL, Lyerly DM, Wilkins TD. The enterotoxin of Bacteroides fragilis is a metalloprotease. Infect Immun. 1995. 63: 175-181.
  4. Rabizadeh S, Rhee KJ, Wu S, Huso D, Gan CM, Golub JE, Wu X, Zhang M, Sears CL. Enterotoxigenic Bacteroides fragilis: A potential instigator of colitis. Inflamm Bowel Dis. 2007. 13: 1475-1483. https://doi.org/10.1002/ibd.20265
  5. Rhee KJ, Wu S, Wu X, Huso DL, Karim B, Franco AA, Rabizadeh S, Golub JE, Mathews LE, Shin J, Sartor RB, Golenbock D, Hamad AR, Gan CM, Housseau F, Sears CL. Induction of persistent colitis by a human commensal, enterotoxigenic Bacteroides fragilis, in wild-type C57BL/6 mice. Infect Immun. 2009. 77: 1708-1718. https://doi.org/10.1128/IAI.00814-08
  6. Roberts AW. G-CSF: a key regulator of neutrophil production, but that's not all! Growth Factors. 2005. 23: 33-41. https://doi.org/10.1080/08977190500055836
  7. Sears CL, Islam S, Saha A, Arjumand M, Alam NH, Faruque AS, Salam MA, Shin J, Hecht D, Weintraub A, Sack RB, Qadri F. Association of enterotoxigenic Bacteroides fragilis infection with inflammatory diarrhea. Clin Infect Dis. 2008. 47: 797-803. https://doi.org/10.1086/591130
  8. Toprak NU, Yagci A, Gulluoglu BM, Akin ML, Demirkalem P, Celenk T, Soyletir G. A possible role of Bacteroides fragilis enterotoxin in the aetiology of colorectal cancer. Clin Microbiol Infect. 2006. 12: 782-786. https://doi.org/10.1111/j.1469-0691.2006.01494.x
  9. Wu S, Lim KC, Huang J, Saidi RF, Sears CL. Bacteroides fragilisenterotoxin cleaves the zonula adherens protein, E-cadherin. Proc Natl Acad Sci U S A. 1998. 95: 14979-14984. https://doi.org/10.1073/pnas.95.25.14979
  10. Wu S, Morin PJ, Maouyo D, Sears CL. Bacteroides fragilis enterotoxin induces c-Myc expression and cellular proliferation. Gastroenterology. 2003. 124: 392-400. https://doi.org/10.1053/gast.2003.50047
  11. Wu S, Powell J, Mathioudakis N, Kane S, Fernandez E, Sears CL. Bacteroides fragilisenterotoxin induces intestinal epithelial cell secretion of interleukin-8 through mitogenactivated protein kinases and a tyrosine kinase-regulated nuclear factor-kB pathway. Infect Immun. 2004. 72: 5832-5839. https://doi.org/10.1128/IAI.72.10.5832-5839.2004
  12. Wu S, Rhee KJ, Albesiano E, Rabizadeh S, Wu X, Yen HR, Huso DL, Brancati FL, Wick E, McAllister F, Housseau F, Pardoll DM, Sears CL. A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses. Nat Med. 2009. 15: 1016-1022. https://doi.org/10.1038/nm.2015
  13. Yim S, Gwon SY, Hwang S, Kim NH, Jung BD, Rhee KJ. Enterotoxigenic Bacteroides fragiliscauses lethal colitis in Mongolian gerbils. Anaerobe. 2013. 21: 64-66. https://doi.org/10.1016/j.anaerobe.2013.03.008