Effect of rebamipide on prostaglandin receptors-mediated increase of inflammatory cytokine production by macrophages. 2003

H Bamba, and S Ota, and A Kato, and H Miyatani, and C Kawamoto, and Y Yoshida, and K Fujiwara
First Department of Internal Medicine, Saitama Medical Center, Saitama Medical School, Saitama, Japan. bam@saitama-med.ac.jp

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.

UI MeSH Term Description Entries
D007378 Interleukins Soluble factors which stimulate growth-related activities of leukocytes as well as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli. Interleukin
D008222 Lymphokines Soluble protein factors generated by activated lymphocytes that affect other cells, primarily those involved in cellular immunity. Lymphocyte Mediators,Mediators, Lymphocyte
D008264 Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.) Bone Marrow-Derived Macrophages,Monocyte-Derived Macrophages,Macrophage,Macrophages, Monocyte-Derived,Bone Marrow Derived Macrophages,Bone Marrow-Derived Macrophage,Macrophage, Bone Marrow-Derived,Macrophage, Monocyte-Derived,Macrophages, Bone Marrow-Derived,Macrophages, Monocyte Derived,Monocyte Derived Macrophages,Monocyte-Derived Macrophage
D011982 Receptors, Prostaglandin Cell surface receptors that bind prostaglandins with high affinity and trigger intracellular changes which influence the behavior of cells. Prostaglandin receptor subtypes have been tentatively named according to their relative affinities for the endogenous prostaglandins. They include those which prefer prostaglandin D2 (DP receptors), prostaglandin E2 (EP1, EP2, and EP3 receptors), prostaglandin F2-alpha (FP receptors), and prostacyclin (IP receptors). Prostaglandin Receptors,Prostaglandin Receptor,Receptor, Prostaglandin,Receptors, Prostaglandins,Prostaglandins Receptors
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000242 Cyclic AMP An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH. Adenosine Cyclic 3',5'-Monophosphate,Adenosine Cyclic 3,5 Monophosphate,Adenosine Cyclic Monophosphate,Adenosine Cyclic-3',5'-Monophosphate,Cyclic AMP, (R)-Isomer,Cyclic AMP, Disodium Salt,Cyclic AMP, Monoammonium Salt,Cyclic AMP, Monopotassium Salt,Cyclic AMP, Monosodium Salt,Cyclic AMP, Sodium Salt,3',5'-Monophosphate, Adenosine Cyclic,AMP, Cyclic,Adenosine Cyclic 3',5' Monophosphate,Cyclic 3',5'-Monophosphate, Adenosine,Cyclic Monophosphate, Adenosine,Cyclic-3',5'-Monophosphate, Adenosine,Monophosphate, Adenosine Cyclic
D000409 Alanine A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases IMMUNITY, and provides energy for muscle tissue, BRAIN, and the CENTRAL NERVOUS SYSTEM. Abufène,Alanine, L-Isomer,L-Alanine,Alanine, L Isomer,L Alanine,L-Isomer Alanine
D000897 Anti-Ulcer Agents Various agents with different action mechanisms used to treat or ameliorate PEPTIC ULCER or irritation of the gastrointestinal tract. This has included ANTIBIOTICS to treat HELICOBACTER INFECTIONS; HISTAMINE H2 ANTAGONISTS to reduce GASTRIC ACID secretion; and ANTACIDS for symptomatic relief. Anti-Ulcer Drugs,Agents, Anti-Ulcer,Anti Ulcer Agents,Anti Ulcer Drugs,Drugs, Anti-Ulcer
D015363 Quinolones A group of derivatives of naphthyridine carboxylic acid, quinoline carboxylic acid, or NALIDIXIC ACID. Ketoquinoline,Ketoquinolines,Oxoquinoline,Oxoquinolines,Quinolinone,Quinolinones,Quinolone
D016207 Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Cytokine

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