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Effect of rebamipide on prostaglandin receptors‐mediated increase of inflammatory cytokine production by macrophages
Author(s) -
Bamba H.,
Ota S.,
Kato A.,
Miyatani H.,
Kawamoto C.,
Yoshida Y.,
Fujiwara K.
Publication year - 2003
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1046/j.1365-2036.18.s1.13.x
Subject(s) - cytokine , receptor , medicine , endocrinology , vascular endothelial growth factor , monocyte , inflammation , u937 cell , prostaglandin , pharmacology , nuclear receptor , chemistry , immunology , biochemistry , vegf receptors , apoptosis , transcription factor , gene
Summary Background : Rebamipide (Reb) is an anti‐ulcer drug, and has unique properties such as anti‐inflammatory action. We previously reported that prostaglandins (PGs) dramatically increased vascular endothelial growth factor (VEGF), a known angiogenic factor and a vascular permeable factor, by activated macrophages through specific PGE receptor and peroxisome proliferator‐activated receptor γ (PPARγ, a nuclear receptor of PG) mediated process. Effects of PGs on the production of other cytokines such as interleukin (IL)‐6 and IL‐8 have been controversial. Aim : To clarify the anti‐inflammatory roles of Reb, we examined the effect of Reb on PGE 1 ‐ and 15‐deoxy‐Δ 12, 14 ‐PGJ 2 (a potent PPARγ ligand, 15d‐PGJ 2 ) ‐induced increase of VEGF production by macrophages. Additionally, effects of these PGs on the production of IL‐6 and IL‐8, and modulation of these actions by Reb were studied. Methods : Phorbol 12‐myristate 13‐acetate‐differentiated U937 cells were used as a human macrophage model (H‐Mac). VEGF, IL‐6, IL‐8 and cAMP were measured by EIA. Results : Reb suppressed PGE 1 ‐, but not 15d‐PGJ 2 ‐, induced increase of VEGF production partially through decrease of cAMP formation. Reb suppressed PGE 1 ‐, but not 15d‐PGJ 2 ‐, induced increase of IL‐6 and IL‐8 production. Conclusion : Reb suppresses membrane, but not nuclear PG receptors mediated increase of inflammatory cytokine production, which may be involved in anti‐ulcer action of this drug.