title: Role of Th-2 cytokines in the development of Barrett's esophagus in rats.
abstract: BACKGROUND
  Barrett's esophagus is characterized by a distinct Th-2-predominant cytokine profile, unlike the pro-inflammatory nature of reflux esophagitis. The aim of this study was to examine the role of Th-2 cytokines during the development of Barrett's esophagus, using a rat model.
  
  
  METHODS
  Barrett's esophagus was induced by Levrat's esophagojejunostomy technique in Brown-Norway (BN) rats. Rats were killed at 8, 15, 30, and 50 weeks after the operation. We studied the incidences of esophagitis and Barrett's esophagus, and the mRNA expression of cytokines and CDX2 by real-time reverse transcriptase-polymerase chain reaction and immunohistochemical staining. Finally, we compared the incidence of Barrett's esophagus in BN rats with that in Sprague-Dawley (SD) rats.
  
  
  RESULTS
  Esophagitis was found in all rats. Barrett's esophagus appeared 8 weeks after the operation, and its incidence and length increased over time. Levels of Th-2 cytokines such as interleukin (IL)-4, IL-10, and IL-13 were significantly increased in Barrett's esophagus as compared to those in non-Barrett's esophagus, while there were no differences in the levels of pro-inflammatory cytokines. The peak of elevated IL-4 mRNA was observed before that of CDX2 mRNA. IL-4 was co-localized in CD4-positive cells and CDX2-positive goblet cells. The incidence of Barrett's esophagus was more common in BN rats (8/10, 80%) than in SD rats (2/7, 28%) at 30 weeks.
  
  
  CONCLUSIONS
  Th-2 cytokines, especially IL-4, may play a crucial role in the development of Barrett's esophagus in an early phase. These results provide understanding of the pathogenesis of Barrett's esophagus from the aspect of the Th-2 immune response.
authors: Department of Gastroenterology, Osaka City University Graduate School of Medicine, 1-4-7 Asahimachi, Abenoku, Osaka, 545-8585, Japan.
authors: Yukie
authors: Y
authors: Kohata
authors: Yasuhiro
authors: Y
authors: Fujiwara
authors: Hirohisa
authors: H
authors: Machida
authors: Hirotoshi
authors: H
authors: Okazaki
authors: Hirokazu
authors: H
authors: Yamagami
authors: Tetsuya
authors: T
authors: Tanigawa
authors: Kenji
authors: K
authors: Watanabe
authors: Toshio
authors: T
authors: Watanabe
authors: Kazunari
authors: K
authors: Tominaga
authors: Min
authors: M
authors: Wei
authors: Hideki
authors: H
authors: Wanibuchi
authors: Tetsuo
authors: T
authors: Arakawa
references: J Pathol. 2005 Nov;207(3):269-76
references: 16177953
references: Dig Dis Sci. 2005 Mar;50(3):425-31
references: 15810620
references: Gastroenterology. 2002 May;122(6):1569-91
references: 12016424
references: Am J Respir Cell Mol Biol. 1997 Apr;16(4):471-8
references: 9115759
references: Gut. 2009 May;58(5):620-8
references: 19136512
references: Gastroenterology. 1994 Sep;107(3):747-54
references: 8076761
references: Am J Physiol. 1997 Feb;272(2 Pt 1):L253-61
references: 9124376
references: Gastroenterology. 2009 Aug;137(2):588-97
references: 19394334
references: Gut. 2008 May;57(5):575-81
references: 18222984
references: J Immunol. 1999 May 15;162(10):6233-7
references: 10229869
references: Clin Cancer Res. 2004 Mar 15;10(6):2020-8
references: 15041721
references: Chest Surg Clin N Am. 2002 Feb;12(1):25-37
references: 11901930
references: Gastroenterology. 2009 Nov;137(5):1776-84
references: 19660463
references: Am J Dig Dis. 1962 Jun;7:564-73
references: 14464730
references: Am J Physiol Gastrointest Liver Physiol. 2008 Sep;295(3):G470-8
references: 18617556
references: J Exp Med. 1998 Mar 16;187(6):939-48
references: 9500796
references: Carcinogenesis. 2000 Aug;21(8):1587-91
references: 10910963
references: Clin Exp Immunol. 2002 Sep;129(3):390-6
references: 12197878
references: Dis Esophagus. 2008;21(1):43-50
references: 18197938
references: Gut. 2002 Apr;50(4):451-9
references: 11889061
references: Gastroenterology. 1996 Nov;111(5):1192-9
references: 8898632
references: Gut. 2006 Jan;55(1):16-25
references: 16118348
references: Gastroenterology. 2003 Mar;124(3):672-82
references: 12612906
references: Am J Gastroenterol. 2008 Mar;103(3):788-97
references: 18341497
references: J Cell Sci. 2002 May 1;115(Pt 9):1783-9
references: 11956310
references: Digestion. 2003;68(4):189-97
references: 14691346
references: Immunol Cell Biol. 2003 Aug;81(4):275-82
references: 12848848
references: J Exp Clin Cancer Res. 2009 Aug 07;28:108
references: 19664209
references: Carcinogenesis. 2007 Feb;28(2):488-96
references: 16990345
references: Gastroenterology. 2010 Jul;139(1):194-203.e1
references: 20303354
references: Am J Pathol. 1999 Apr;154(4):965-73
references: 10233832
references: Cancer Res. 1989 Dec 1;49(23):6803-8
references: 2819720
references: Am J Physiol Gastrointest Liver Physiol. 2008 Aug;295(2):G211-8
references: 18556417
references: J Gastrointest Surg. 2007 Jul;11(7):827-34
references: 17458588
references: J Gastrointest Surg. 2007 Jul;11(7):869-74
references: 17440788