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Byline: K. Noguchi (1), K. Iwasaki (1), I. Ishikawa (1) Abstract: In the present study, the effect of prostaglandin E.sub.2 (PGE.sub.2) on intercellular adhesion molecule-1 (ICAM-1) expression in interferon-I3 (IFN-I3)-stimulated human gingival fibroblasts (HGF) was investigated. Addition of PGE.sub.2 to HGF inhibited ICAM-1 expression elicited by IFN-I3. As PGE.sub.2 elevated intercellular cyclic AMP (cAMP) levels in HGF in a dose-dependent fashion, the effect of dibutyryl cAMP and 8-bromo-cAMP, cAMP analogues, on IFN-I3-elicited ICAM-1 expression was examined. Both the agents downregulated ICAM-1 expression in IFN-I3-stimulated HGF. Next, we examined which subtype(s) of the four PGE.sub.2 receptor subtypes (EP.sub.1, EP.sub.2, EP.sub.3 and EP.sub.4) modulated the ICAM-1 expression elicited by IFN-I3, using subtype-specific agonists or antagonists. An EP.sub.2/EP.sub.4 agonist, 11-deoxy-PGE.sub.1, attenuated IFN-I3-elicited ICAM-1 expression in a concentration-dependent manner. A specific EP.sub.4 antagonist, AH-23848B, showed no effect on inhibition of IFN-I3-elicited ICAM-1 expression by PGE.sub.2 and 11-deoxy-PGE.sub.1. Butaprost, an EP.sub.2-selective agonist, mimicked inhibition of IFN-I3-elicited ICAM-1 expression by 11-deoxy-PGE.sub.1. An EP.sub.3 agonist, ONO-AP-324, was inert with respect to IFN-I3-elicited ICAM-1 expression. Sulprostone, an EP.sub.1/EP.sub.3 agonist, showed stimulatory effect on ICAM-1 expression elicited by IFN-I3. From these results, we suggest that PGE.sub.2 downregulates IFN-I3-induced ICAM-1 expression in HGF, primarily via EP.sub.2 receptors by cAMP-dependent signaling pathways. Author Affiliation: (1) Department of Periodontology, Graduate School, Faculty of Dentistry, Tokyo Medical and Dental University, 1--5--45, Yushima, Bunkyo-ku, Tokyo, 113--8549, Japan Article History: Registration Date: 30/09/2004

Byline: Noriko Sugita (1), Asako Kimura (1,2), Yutaka Matsuki (1), Tadashi Yamamoto (2), Hiromasa Yoshie (1), Kohji Hara (1) Abstract: DNA binding activity of NF-IoB and AP-1 were examined in neutrophils stimulated with LPS purified from P. gingivalis, a major pathogenic bacteria of periodontitis lesion. Porphyromonas gingivalis LPS enhanced the activity reaching a peak at a concentration of 500 ng/ml in the absence of serum. The NF-IoB activation stimulated with 10 ng/ml of P. gingivalis LPS was suppressed approximately 44% by treatment of neutrophils with anti-CD14 antibody under the presence of serum. Increase in the steady-state IL-8 mRNA level was concomitantly observed by stimulation of neutrophils with 500 ng/ml of P. gingivalis LPS under the absence of serum. These results indicate that P. gingivalis LPS activates NF-IoB and AP-1 in both serum-dependent and -independent manners, followed by increased IL-8 transcription in neutrophils, and suggested a role for P. gingivalis LPS in IL-8 synthesis by neutrophils in inflamed gingiva and GCF. Author Affiliation: (1) Department of Periodontology, Niigata University School of Dentistry, Japan (2) Institute of Nephrology, Niigata University School of Medicine, Japan Article History: Registration Date: 03/10/2004