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Am J Physiol Gastrointest Liver Physiol (October 8, 2009). doi:10.1152/ajpgi.00240.2009
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Research Article

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

Hisayuki Matsunaga,1 Ryota Hokari,1,* Masaaki Higashiyama,1 Chie Kurihara,2 Yoshikiyo Okada,2 Chikako Watanabe,3 Shunsuke Komoto,2 Mitsuyasu Nakamura,1 Atsushi Kawaguchi,2 Shigeaki Nagao,2 and Soichiro Miura1

1National Defense Medical College 2 3keio university

Submitted 22 June 2009 ; revision received 8 September 2009 ; accepted in final form 5 October 2009

ABSTRACT

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 PDE3 inhibitor of platelets decreases monocytes recruitment to inteastinal 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 weeks of age after piroxicam treatment for 3 weeks. 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 weeks significantly attenuated the increase in intestinal weight and the histological changes, including invasion of F4/80(+)-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, indicating a potential usefulness of anti-platelet drugs for treatment of Crohn's disease.

PDE-3; mice; monocytes; platelets


* National Defense Medical College ryota{at}ndmc.ac.jp






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