Cilostazol, a specific PDE-3 inhibitor, ameliorates chronic ileitis via suppression of interaction of platelets with monocytes.
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.
Matsunaga
Hisayuki
H
Dept. of Internal Medicine, National Defense Medical College, Saitama, Japan.
Hokari
Ryota
R
Higashiyama
Masaaki
M
Kurihara
Chie
C
Okada
Yoshikiyo
Y
Watanabe
Chikako
C
Komoto
Shunsuke
S
Nakamura
Mitsuyasu
M
Kawaguchi
Atsushi
A
Nagao
Shigeaki
S
Miura
Soichiro
S
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology; D002465:Cell Movement / Q000187:drug effects; D002908:Chronic Disease; D000077407:Cilostazol; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3 / Q000378:metabolism; D004195:Disease Models, Animal; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D007079:Ileitis / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D007082:Ileum / Q000098:blood supply / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D051379:Mice; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D019007:P-Selectin / Q000378:metabolism; D058987:Phosphodiesterase 3 Inhibitors; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010894:Piroxicam; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013777:Tetrazoles / Q000494:pharmacology*; D013997:Time Factors; D014699:Venules / Q000187:drug effects / Q000276:immunology
D000893:Anti-Inflammatory Agents; D005765:Gastrointestinal Agents; D019007:P-Selectin; D058987:Phosphodiesterase 3 Inhibitors; D010726:Phosphodiesterase Inhibitors; D010975:Platelet Aggregation Inhibitors; D013777:Tetrazoles; D010894:Piroxicam; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D000077407:Cilostazol