PMID- 10697805
OWN - NLM
STAT- MEDLINE
DCOM- 20000315
LR  - 20190905
IS  - 0022-3484 (Print)
IS  - 0022-3484 (Linking)
VI  - 34
IP  - 8
DP  - 1999 Nov
TI  - Prostaglandin E2 receptors of the EP2 and EP4 subtypes downregulate tumor 
      necrosis factor alpha-induced intercellular adhesion molecule-1 expression in 
      human gingival fibroblasts.
PG  - 478-85
AB  - Prostaglandin E2 (PGE2) exerts its biological actions via EP receptors, which are 
      divided into 4 subtypes of EP1, EP2, EP3 and EP4. In the present study, we 
      investigated whether PGE2 regulated intercellular adhesion molecule-1 (ICAM-1) 
      expression in human gingival fibroblasts (HGF) stimulated with tumor necrosis 
      factor-alpha (TNF alpha) and if so, which subtype(s) of PGE2 receptors was 
      involved. Exogenous addition of PGE2 to HGF inhibited ICAM-1 expression elicited 
      by TNF alpha in a concentration-dependent manner. Treatment of HGF with 
      indomethacin, a cyclo-oxygenase inhibitor, had no effect on TNF alpha-elicited 
      ICAM-1 expression, although indomethacin completely inhibited PGE2 production 
      enhanced by TNF alpha. Next, we examined which subtype(s) of the 4 EP receptors 
      modulated the ICAM-1 expression elicited by TNF alpha, using subtype-specific 
      agonists and antagonists. 11-deoxy-PGE1, a selective EP2/EP4 agonist, inhibited 
      TNF alpha-elicited ICAM-1 expression as potently as PGE2, while butaprost, a 
      selective EP2 agonist, was somewhat less effective than PGE2. AH23848B, an EP4 
      antagonist, antagonized the inhibitory effect of TNF alpha-elicited ICAM-1 
      expression by PGE2. Sulprostone, an EP1/EP3 agonist, and ONO-AP-324, an EP3 
      agonist, were inert to TNF alpha-elicited ICAM-1 expression. As EP2 and EP4 
      receptors are linked to elevation of intracellular cyclic AMP (cAMP), the effect 
      of dibutyryl cAMP and 8-bromo-cAMP, cAMP analogs, on TNF alpha-elicited ICAM-1 
      expression was examined. Both the agents downregulated ICAM-1 expression in TNF 
      alpha-stimulated HGF. From these data, we suggest that PGE2 downregulates TNF 
      alpha-induced ICAM-1 expression in HGF, via EP2 and EP4 receptors by 
      cAMP-dependent signaling pathways, which may result in control of inflammatory 
      and immunological responses in periodontal disease.
FAU - Noguchi, K
AU  - Noguchi K
AD  - Department of Periodontology, Faculty of Dentistry, Tokyo Medical and Dental 
      University, Japan. kazuyuki-noguchi.peri@dent.tmd.ac.jp
FAU - Iwasaki, K
AU  - Iwasaki K
FAU - Shitashige, M
AU  - Shitashige M
FAU - Ishikawa, I
AU  - Ishikawa I
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Periodontal Res
JT  - Journal of periodontal research
JID - 0055107
RN  - 0 (PTGER2 protein, human)
RN  - 0 (PTGER4 protein, human)
RN  - 0 (Receptors, Prostaglandin E)
RN  - 0 (Receptors, Prostaglandin E, EP2 Subtype)
RN  - 0 (Receptors, Prostaglandin E, EP4 Subtype)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - K7Q1JQR04M (Dinoprostone)
SB  - IM
MH  - Analysis of Variance
MH  - Cell Culture Techniques/methods
MH  - Cells, Cultured
MH  - Dinoprostone/*metabolism
MH  - Dose-Response Relationship, Drug
MH  - Down-Regulation/drug effects/*physiology
MH  - Fibroblasts/drug effects/metabolism
MH  - Gingiva/cytology/drug effects/*metabolism
MH  - Humans
MH  - Immunohistochemistry
MH  - Intercellular Adhesion Molecule-1/drug effects/*metabolism
MH  - Receptors, Prostaglandin E/drug effects/*metabolism
MH  - Receptors, Prostaglandin E, EP2 Subtype
MH  - Receptors, Prostaglandin E, EP4 Subtype
MH  - Stimulation, Chemical
MH  - Time Factors
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 2000/03/04 09:00
MHDA- 2000/03/18 09:00
CRDT- 2000/03/04 09:00
PHST- 2000/03/04 09:00 [pubmed]
PHST- 2000/03/18 09:00 [medline]
PHST- 2000/03/04 09:00 [entrez]
AID - 10.1111/j.1600-0765.1999.tb02284.x [doi]
PST - ppublish
SO  - J Periodontal Res. 1999 Nov;34(8):478-85. doi: 
      10.1111/j.1600-0765.1999.tb02284.x.