Cilostazol, a specific PDE-3 inhibitor, ameliorates chronic ileitis via suppression of interaction of platelets with monocytes.

نویسندگان

  • Hisayuki Matsunaga
  • Ryota Hokari
  • Masaaki Higashiyama
  • Chie Kurihara
  • Yoshikiyo Okada
  • Chikako Watanabe
  • Shunsuke Komoto
  • Mitsuyasu Nakamura
  • Atsushi Kawaguchi
  • Shigeaki Nagao
  • Soichiro Miura
چکیده

Excessive migration of monocytes to a site of intestinal inflammation contributes to tissue damage in Crohn's disease. It is known that cilostazol, a specific phosphodiesterase-3 (PDE-3) inhibitor of platelets, decreases monocyte recruitment to intestinal mucosa through suppression of platelet-monocyte interactions. The objective of this study was to clarify whether cilostazol ameliorates murine ileitis by suppression of monocyte migration. Significant inflammation was induced in the ileum of SAMP1/Yit mice at 23 wk of age after piroxicam treatment for 3 wk. Weight of the terminal ileum of mice was significantly greater with inflammatory cell infiltration in SAMP1/Yit mice than in control mice (AKR-J). Treatment of SAMP1/Yit mice with cilostazol-containing food (200 ppm) for 3 wk significantly attenuated the increase in intestinal weight and the histological changes, including invasion of F4/80-positive macrophages. A significant increase in migration of monocytes and platelets to microvessels of the ileal mucosa was observed in SAMP/Yit mice in vivo by using an intravital fluorescence microscope. Pretreatment with cilostazol significantly attenuated the increased migration of monocytes, possibly through suppression of platelet-monocyte interactions. In conclusion, a PDE-3 inhibitor ameliorates murine ileitis through attenuating migration of monocytes to the intestinal mucosa, suggesting a potential usefulness of antiplatelet drugs for treatment of Crohn's disease.

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عنوان ژورنال:
  • American journal of physiology. Gastrointestinal and liver physiology

دوره 297 6  شماره 

صفحات  -

تاریخ انتشار 2009