Effect of rebamipide on prostaglandin receptors-mediated increase of inflammatory cytokine production by macrophages.
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 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.


OBJECTIVE
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.


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 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.


CONCLUSIONS
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.
Bamba
H
H
First Department of Internal Medicine, Saitama Medical Center, Saitama Medical School, Saitama, Japan. bam@saitama-med.ac.jp
Ota
S
S
Kato
A
A
Miyatani
H
H
Kawamoto
C
C
Yoshida
Y
Y
Fujiwara
K
K
D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis*; D016228:Endothelial Growth Factors / Q000096:biosynthesis; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis; D008222:Lymphokines / Q000096:biosynthesis; D008264:Macrophages / Q000378:metabolism*; D015363:Quinolones / Q000494:pharmacology*; D011982:Receptors, Prostaglandin / Q000187:drug effects / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000897:Anti-Ulcer Agents; D016207:Cytokines; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D007378:Interleukins; D008222:Lymphokines; D015363:Quinolones; D011982:Receptors, Prostaglandin; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000242:Cyclic AMP; C052785:rebamipide; D000409:Alanine