Cilostazol, a specific PDE-3 inhibitor, ameliorates chronic ileitis via suppression of interaction of platelets with monocytes
| Autor: | Masaaki Higashiyama, Hisayuki Matsunaga, Chikako Watanabe, Yoshikiyo Okada, Chie Kurihara, Shunsuke Komoto, Mitsuyasu Nakamura, Shigeaki Nagao, Atsushi Kawaguchi, Soichiro Miura, Ryota Hokari |
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| Rok vydání: | 2009 |
| Předmět: |
Blood Platelets
Time Factors P-selectin Phosphodiesterase Inhibitors Physiology Anti-Inflammatory Agents Tetrazoles Inflammation Pharmacology Biology Phosphodiesterase 3 Inhibitors Monocytes Mice Piroxicam Gastrointestinal Agents Venules Intestinal mucosa Cell Movement Ileum Physiology (medical) medicine Animals Ileitis Gastrointestinal agent Hepatology Monocyte Gastroenterology medicine.disease Cyclic Nucleotide Phosphodiesterases Type 3 Cilostazol Disease Models Animal P-Selectin medicine.anatomical_structure Chronic Disease Immunology Platelet aggregation inhibitor medicine.symptom Platelet Aggregation Inhibitors medicine.drug |
| Zdroj: | American Journal of Physiology-Gastrointestinal and Liver Physiology. 297:G1077-G1084 |
| ISSN: | 1522-1547 0193-1857 |
| DOI: | 10.1152/ajpgi.00240.2009 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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