International Journal of Colorectal Disease

, Volume 26, Issue 11, pp 1453–1462 | Cite as

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

  • Yoshiaki Hayashi
  • Kenta Narumi
  • Shigetsugu Tsuji
  • Toshinari Tsubokawa
  • Masa-aki Nakaya
  • Tomohiko Wakayama
  • Masahiko Zuka
  • Tohru Ohshima
  • Masakazu Yamagishi
  • Toshihide Okada
Original Article

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.

Keywords

Adrenomedullin Dextran sulfate sodium-induced ulcerative colitis Cytokine 

Notes

Acknowledgments

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

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Yoshiaki Hayashi
    • 1
  • Kenta Narumi
    • 1
  • Shigetsugu Tsuji
    • 1
  • Toshinari Tsubokawa
    • 1
  • Masa-aki Nakaya
    • 2
  • Tomohiko Wakayama
    • 2
  • Masahiko Zuka
    • 3
  • Tohru Ohshima
    • 3
  • Masakazu Yamagishi
    • 1
  • Toshihide Okada
    • 1
  1. 1.Department of Internal MedicineKanazawa University Graduate School of MedicineKanazawaJapan
  2. 2.Department of Histology and EmbryologyKanazawa University Graduate School of MedicineKanazawaJapan
  3. 3.Department of Forensic and Social Environmental MedicineKanazawa University Graduate School of MedicineKanazawaJapan

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