title: Effect of rebamipide on prostaglandin receptors-mediated increase of inflammatory cytokine production by macrophages.
abstract: 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.
authors.affiliation: First Department of Internal Medicine, Saitama Medical Center, Saitama Medical School, Saitama, Japan. bam@saitama-med.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Bamba
authors.forename: S
authors.initials: S
authors.lastname: Ota
authors.forename: A
authors.initials: A
authors.lastname: Kato
authors.forename: H
authors.initials: H
authors.lastname: Miyatani
authors.forename: C
authors.initials: C
authors.lastname: Kawamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Yoshida
authors.forename: K
authors.initials: K
authors.lastname: Fujiwara
mesh_terms: 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
chemical_list: 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