title: BTB and CNC homolog 1 (Bach1) deficiency ameliorates TNBS colitis in mice: role of M2 macrophages and heme oxygenase-1.
abstract: BACKGROUND
  BTB and CNC homolog 1 (Bach1) is a transcriptional repressor of heme oxygenase-1 (HO-1), which plays an important role in the protection of cells and tissues against acute and chronic inflammation. However, the role of Bach1 in the gastrointestinal mucosal defense system remains little understood. HO-1 supports the suppression of experimental colitis and localizes mainly in macrophages in colonic mucosa. This study was undertaken to elucidate the Bach1/HO-1 system's effects on the pathogenesis of experimental colitis.
  
  
  METHODS
  This study used C57BL/6 (wild-type) and homozygous Bach1-deficient C57BL/6 mice in which colonic damage was induced by the administration of an enema of 2,4,6-trinitrobenzene sulfonic acid (TNBS). Subsequently, they were evaluated macroscopically, histologically, and biochemically. Peritoneal macrophages from the respective mice were isolated and analyzed. Then, wild-type mice were injected with peritoneal macrophages from the respective mice. Acute colitis was induced similarly.
  
  
  RESULTS
  TNBS-induced colitis was inhibited in Bach1-deficient mice. TNBS administration increased the expression of HO-1 messenger RNA and protein in colonic mucosa in Bach1-deficient mice. The expression of HO-1 mainly localized in F4/80-immunopositive and CD11b-immunopositive macrophages. Isolated peritoneal macrophages from Bach1-deficient mice highly expressed HO-1 and also manifested M2 macrophage markers, such as Arginase-1, Fizz-1, Ym1, and MRC1. Furthermore, TNBS-induced colitis was inhibited by the transfer of Bach1-deficient macrophages into wild-type mice.
  
  
  CONCLUSIONS
  Deficiency of Bach1 ameliorated TNBS-induced colitis. Bach1-deficient macrophages played a key role in protection against colitis. Targeting of this mechanism is applicable to cell therapy for human inflammatory bowel disease.
authors: Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors: Akihito
authors: A
authors: Harusato
authors: Yuji
authors: Y
authors: Naito
authors: Tomohisa
authors: T
authors: Takagi
authors: Kazuhiko
authors: K
authors: Uchiyama
authors: Katsura
authors: K
authors: Mizushima
authors: Yasuko
authors: Y
authors: Hirai
authors: Yasuki
authors: Y
authors: Higashimura
authors: Kazuhiro
authors: K
authors: Katada
authors: Osamu
authors: O
authors: Handa
authors: Takeshi
authors: T
authors: Ishikawa
authors: Nobuaki
authors: N
authors: Yagi
authors: Satoshi
authors: S
authors: Kokura
authors: Hiroshi
authors: H
authors: Ichikawa
authors: Akihiko
authors: A
authors: Muto
authors: Kazuhiko
authors: K
authors: Igarashi
authors: Toshikazu
authors: T
authors: Yoshikawa
mesh_terms: D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000037:antagonists & inhibitors / Q000502:physiology*; D015415:Biomarkers / Q000032:analysis; D003092:Colitis / Q000139:chemically induced / Q000517:prevention & control*; D051547:Heme Oxygenase-1 / Q000502:physiology*; D006801:Humans; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009195:Peroxidase / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity*
chemical_list: C486316:Bach1 protein, mouse; D050976:Basic-Leucine Zipper Transcription Factors; D015415:Biomarkers; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse