title: Apoptosis inhibitor expressed by macrophages tempers autoimmune colitis and the risk of colitis-based carcinogenesis in TCRalpha-/- mice.
abstract: BACKGROUND
  Crohn's disease and ulcerative colitis (UC) are the two main entities involved in human inflammatory bowel disease (IBD). However, their precise etiologies remain unclear. To study the development of mucosal inflammation, and chronic inflammation-based dysplasia and carcinoma formation, we examined possible roles of the apoptosis inhibitor expressed by macrophages (AIM) in an experimental IBD model.
  
  
  METHODS
  In this study, we used T cell receptor alpha deficient (TCRalpha(-/-)) mice, a known UC-like colitis model. We generated TCRalpha(-/-) x AIM(-/-) double knockout mice by crossbreeding TCRalpha(-/-) with AIM(-/-) mice. At 24 weeks of age, mice were killed to obtain colon tissues for pathological examinations. TCRalpha(-/-) x AIM(+/-) mice, heterozygous littermates of TCRalpha(-/-) x AIM(-/-) mice, were used as controls.
  
  
  RESULTS
  Severe colitis was observed in TCRalpha(-/-) x AIM(-/-) mice, when compared with TCRalpha(-/-) x AIM(+/-) mice. Dysplasia was detected in TCRalpha(-/-) x AIM(-/-) mice, but not in TCRalpha(-/-) x AIM(+/-) mice. Adenocarcinoma formation was observed from dysplasia only in TCRalpha(-/-) x AIM(-/-) mice.
  
  
  CONCLUSIONS
  Not only a high incidence of severe colitis but also dysplasia and adenocarcinoma formation were observed in TCRalpha(-/-) x AIM(-/-) mice only. AIM have some regulatory roles in inflammation and progression of dysplasia to carcinoma in TCRalpha(-/-) mice.
authors.affiliation: Department of Medicine and Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan. haruta@ige.twmu.ac.jp
authors.forename: Ikuko
authors.initials: I
authors.lastname: Haruta
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Shibata
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Kato
authors.forename: Masanori
authors.initials: M
authors.lastname: Tanaka
authors.forename: Makio
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Oguma
authors.forename: Keiko
authors.initials: K
authors.lastname: Shiratori
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000378:metabolism* / Q000473:pathology; D016466:CHO Cells; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000276:immunology / Q000378:metabolism*; D003093:Colitis, Ulcerative / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D051034:Inhibitor of Apoptosis Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000172:deficiency* / Q000235:genetics*; D012307:Risk Factors
chemical_list: D051034:Inhibitor of Apoptosis Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta