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Impact of adrenomedullin on dextran sulfate sodium-induced inflammatory colitis in mice: insights from in vitro and in vivo experimental studies

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Abstract

Background

Although adrenomedullin (AM) is known to ameliorate inflammatory processes, few data exist regarding the effect of AM on inflammatory colitis. Therefore, we examined the effect of AM on inflammatory response in vitro and in vivo colitis model.

Methods

In mice experimental colitis induced by 3% dextran sulfate sodium (DSS) in drinking water for 7 days, AM with 225–900 μg/kg in 0.5 ml of saline or saline alone were given intraperitoneally once a day. In the in vitro experiment, we determined the cytokine response in THP-1 cell activated by lipopolysaccharide with or without AM of 10 nM. Additionally, we performed wound healing assay in Caco-2 cell interfered by DSS with or without AM of 100 nM.

Results

In the colitis model, AM significantly reduced the disease activity index, histological score, and local production of inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in accordance with reduction of serum amyloid A levels. Secretion of TNF-α in lipopolysaccharide-stimulated THP-1 cells was significantly reduced in the presence of AM. The distance of wound healing interfered by 0.25% DSS was significantly improved in the presence of AM of 100 nM.

Conclusions

These results demonstrate that AM could ameliorate DSS-induced experimental colitis possibly through suppression of systemic and local production of cytokines such as TNF-α, associated with acceleration of ulcer reepithelialization and colon tissue regeneration.

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Acknowledgments

The authors wish to express their thanks to Dr. Kenji Kangawa, National Cardiovascular Center Research Institute, Suita, Japan, for kindly providing AM.

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Kanazawa University Graduate School of Medicine, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan

    Yoshiaki Hayashi, Kenta Narumi, Shigetsugu Tsuji, Toshinari Tsubokawa, Masakazu Yamagishi & Toshihide Okada

  2. Department of Histology and Embryology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan

    Masa-aki Nakaya & Tomohiko Wakayama

  3. Department of Forensic and Social Environmental Medicine, Kanazawa University Graduate School of Medicine, Kanazawa, Japan

    Masahiko Zuka & Tohru Ohshima

Authors
  1. Yoshiaki Hayashi
  2. Kenta Narumi
  3. Shigetsugu Tsuji
  4. Toshinari Tsubokawa
  5. Masa-aki Nakaya
  6. Tomohiko Wakayama
  7. Masahiko Zuka
  8. Tohru Ohshima
  9. Masakazu Yamagishi
  10. Toshihide Okada

Corresponding author

Correspondence toMasakazu Yamagishi.

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Hayashi, Y., Narumi, K., Tsuji, S.et al. Impact of adrenomedullin on dextran sulfate sodium-induced inflammatory colitis in mice: insights from in vitro and in vivo experimental studies.Int J Colorectal Dis26, 1453–1462 (2011). https://doi.org/10.1007/s00384-011-1254-0

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