Bamba H, Ota S, Kato A, Miyatani H, Kawamoto C, Yoshida Y, Fujiwara K
First Department of Internal Medicine, Saitama Medical Center, Saitama Medical School, Saitama, Japan.
Aliment Pharmacol Ther. 2003 Jul;18 Suppl 1:113-8. doi: 10.1046/j.1365-2036.18.s1.13.x.
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 gamma (PPARgamma, 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.
To clarify the anti-inflammatory roles of Reb, we examined the effect of Reb on PGE1- and 15-deoxy-Delta12, 14-PGJ2 (a potent PPARgamma ligand, 15d-PGJ2) -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.
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.
Reb suppressed PGE1-, but not 15d-PGJ2-, induced increase of VEGF production partially through decrease of cAMP formation. Reb suppressed PGE1 -, but not 15d-PGJ2-, induced increase of IL-6 and IL-8 production.
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.
瑞巴派特（Reb）是一种抗溃疡药物，具有抗炎等独特特性。我们之前报道过，前列腺素（PGs）通过激活的巨噬细胞，经特定的前列腺素E受体和过氧化物酶体增殖物激活受体γ（PPARγ，一种PG的核受体）介导的过程，显著增加血管内皮生长因子（VEGF，一种已知的血管生成因子和血管通透因子）的水平。PGs对其他细胞因子如白细胞介素（IL）-6和IL-8产生的影响一直存在争议。
为阐明瑞巴派特的抗炎作用，我们研究了瑞巴派特对巨噬细胞中PGE1和15-脱氧-Δ12,14-前列腺素J2（一种有效的PPARγ配体，15d-PGJ2）诱导的VEGF产生增加的影响。此外，还研究了这些PGs对IL-6和IL-8产生的影响，以及瑞巴派特对这些作用的调节。
将佛波酯分化的U937细胞用作人巨噬细胞模型（H-Mac）。通过酶免疫测定法测量VEGF、IL-6、IL-8和cAMP。
瑞巴派特部分通过减少cAMP形成，抑制PGE1诱导的VEGF产生增加，但不抑制15d-PGJ2诱导的增加。瑞巴派特抑制PGE1诱导的IL-6和IL-8产生增加，但不抑制15d-PGJ2诱导的增加。
瑞巴派特抑制膜性而非核性PG受体介导的炎性细胞因子产生增加，这可能与该药物的抗溃疡作用有关。
