Prostaglandins E2 and I2 downregulate tumor necrosis factor alpha-induced intercellular adhesion molecule-1 expression in human oral gingival epithelial cells.
In the present study, we examined whether prostaglandin (PG) E2 and PGI2 regulated intercellular adhesion molecule-1 (ICAM-1) expression in human oral gingival epithelial cells stimulated with tumor necrosis factor alpha (TNF alpha). TNF alpha potently induced ICAM-1 expression in a dose- and time-dependent fashion. PGE2 and carbacyclin (a stable analogue of PGI2) significantly decreased ICAM-1 expression in TNF alpha-challenged oral gingival epithelial cells. Next, of the four subtypes of PGE2 receptors (EP1, EP2, EP3 and EP4), we examined which subtype(s) mediated inhibition of TNF alpha-induced ICAM-1 expression by PGE2. 11-deoxy-PGE2, an EP2/EP4 agonist, significantly suppressed TNF alpha-induced ICAM-1 expression, whereas butaprost, an EP2 agonist, sulprostone, an EP1/EP3 agonist, and ONO-AP-324, an EP3 agonist, caused no effect on it. By reverse transcriptase-polymerase chain reaction, expression of EP4 mRNA was detected in oral gingival epithelial cells. Dibutyryl cAMP, a cAMP analogue, and forskolin, a direct activator of adenylate cyclase, significantly inhibited TNF alpha-induced ICAM-1 expression in oral gingival epithelial cells. From these results, we suggest that PGE2 and PGI2 inhibit TNF alpha-elicited ICAM-1 expression by cAMP-dependent pathways via EP4 receptors and IP receptors, respectively.
Noguchi
K
K
Department of Periodontology, Faculty of Dentistry, Tokyo Medical & Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
Iwasaki
K
K
Endo
H
H
Kondo
H
H
Shitashige
M
M
Ishikawa
I
I
D000085:Acetates / Q000494:pharmacology; D000328:Adult; D000527:Alprostadil / Q000031:analogs & derivatives* / Q000494:pharmacology; D000704:Analysis of Variance; D001559:Benzhydryl Compounds / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D015232:Dinoprostone / Q000819:agonists / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects* / Q000235:genetics; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011464:Epoprostenol / Q000031:analogs & derivatives / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D005881:Gingiva / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects / Q000235:genetics*; D018078:Receptors, Prostaglandin E / Q000819:agonists / Q000145:classification / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000085:Acetates; D001559:Benzhydryl Compounds; C117875:ONO AP 324; D018078:Receptors, Prostaglandin E; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D005576:Colforsin; C016767:sulprostone; D003994:Bucladesine; C026678:carboprostacyclin; D011464:Epoprostenol; D000527:Alprostadil; C048491:butaprost; D015232:Dinoprostone