Prostaglandin E2 inhibits IL-18-induced ICAM-1 and B7.2 expression through EP2/EP4 receptors in human peripheral blood mononuclear cells

Hideo K. Takahashi, Hiromi Iwagaki, Tadashi Yoshino, Shuji Mori, Toshihiko Morichika, Hideyuki Itoh, Minori Yokoyama, Shinichiro Kubo, Eisaku Kondo, Tadaatsu Akagi, Noriaki Tanaka, Masahiro Nishibori

Research output: Contribution to journalArticlepeer-review

69 Citations (Scopus)

Abstract

Costimulatory molecules play important roles in immune responses. In the present study we investigated the effects of PGE2 on the expression of ICAM-1, B7.1, and B7.2 on monocytes in IL-18-stimulated PBMC using FACS analysis. Addition of PGE2 to PBMC inhibited ICAM-1 and B7.2 expression elicited by IL-18 in a concentration-dependent manner. We examined the involvement of four subtypes of PGE2 receptors, EP1, EP2, EP3, and EP4, in the modulatory effect of PGE2, on ICAM-1 and B7.2 expression elicited by IL-18, using subtype-specific agonists. ONO-AE1-259-01 (EP2R agonist) inhibited IL-18-elicited ICAM-1 and B7.2 expression in a concentration-dependent manner with a potency slightly less than that of PGE2, while ONO-AE1-329 (EP4R agonist) was much less potent than PGE2. The EP2/EP4R agonist 11-deoxy-PGE1-mimicked the effect of PGE2 with the same potency. ONO-D1-004 (EP1R agonist) and ONO-AE-248 (EP3R agonist) showed no effect on IL-18-elicited ICAM-1 or B7.2 expression. These results indicated that EP2 and EP4Rs were involved in the action of PGE2. Dibutyryl cAMP and forskolin down-regulated ICAM-1 and B7.2 expression in IL-18-stimulated monocytes. As EP2 and EP4Rs are coupled to adenylate cyclase, we suggest that PGE2 down-regulates IL-18-induced ICAM-1 and B7.2 expression in monocytes via EP2 and EP4Rs by cAMP-dependent signaling pathways. The fact that anti-B7.2 as well as anti-ICAM-1 Ab inhibited IL-18-induced cytokine production implies that PGE2 may modulate the immune response through regulation of the expression of particular adhesion molecules on monocytes via EP2 and EP4Rs.

Original languageEnglish
Pages (from-to)4446-4454
Number of pages9
JournalJournal of Immunology
Volume168
Issue number9
DOIs
Publication statusPublished - May 1 2002

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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