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Role of Th-2 cytokines in the development of Barrett’s esophagus in rats

  • Original Article—Alimentary Tract
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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.

Conclusion

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.

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Acknowledgments

This study was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

Conflict of interest

No conflicts of interest exist.

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Authors and Affiliations

  1. Department of Gastroenterology, Osaka City University Graduate School of Medicine, 1-4-7 Asahimachi, Abenoku, Osaka, 545-8585, Japan

    Yukie Kohata, Yasuhiro Fujiwara, Hirohisa Machida, Hirotoshi Okazaki, Hirokazu Yamagami, Tetsuya Tanigawa, Kenji Watanabe, Toshio Watanabe, Kazunari Tominaga & Tetsuo Arakawa

  2. Department of Pathology, Osaka City University Graduate School of Medicine, Osaka, Japan

    Min Wei & Hideki Wanibuchi

Authors
  1. Yukie Kohata
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  2. Yasuhiro Fujiwara
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  3. Hirohisa Machida
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Correspondence to Yasuhiro Fujiwara.

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Kohata, Y., Fujiwara, Y., Machida, H. et al. Role of Th-2 cytokines in the development of Barrett’s esophagus in rats. J Gastroenterol 46, 883–893 (2011). https://doi.org/10.1007/s00535-011-0405-y

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  • DOI: https://doi.org/10.1007/s00535-011-0405-y

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