EP4 agonist inhibits lipopolysaccharide-induced mucus secretion in airway epithelial cells.
OBJECTIVE
We examined the in vivo effects of agonists for prostaglandin E2 receptors (EP1, EP2, EP3, and EP4) on mucus hypersecretion. We also examined the in vitro effects of EP agonists on airway epithelial cells.


METHODS
For the in vivo study, we induced hypertrophic and metaplastic changes of goblet cells in rat nasal epithelium by intranasal lipopolysaccharide (LPS) instillation. For the in vitro study, we used NCI-H292 cells and cultured human nasal epithelial cells.


RESULTS
Subcutaneous injection of the EP4 agonist (1 to 100 microg/kg) dose-dependently inhibited LPS-induced mucus production and neutrophil infiltration. The EP3 agonist (100 microg/kg) also had some inhibitory effects on mucus production, whereas the EP1 and EP2 agonists showed no effect. The LPS-induced mucus secretion was significantly inhibited by the EP3 and EP4 agonists at 10(-6) mol/L in cultured epithelial cells. The LPS-induced interleukin-8 secretion was also inhibited by the EP3 and EP4 agonists.


CONCLUSIONS
These results indicate that the EP4 agonist inhibited LPS-induced airway mucus hypersecretion directly or indirectly through the suppression of interleukin-8 secretion and neutrophil infiltration.
Hattori
Reiko
R
Department of Otorhinolaryngology-Head and Neck Surgery, Mie University School of Medicine, Tsu, Japan.
Shimizu
Shino
S
Majima
Yuichi
Y
Shimizu
Takeshi
T
D000818:Animals; D018277:Carcinoma, Mucoepidermoid / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D015232:Dinoprostone / Q000031:analogs & derivatives / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D020397:Goblet Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D009093:Mucus / Q000187:drug effects / Q000378:metabolism*; D009297:Nasal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009669:Nose Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012334:RNA, Neoplasm / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D018078:Receptors, Prostaglandin E / Q000819:agonists* / Q000096:biosynthesis / Q000235:genetics; D058309:Receptors, Prostaglandin E, EP4 Subtype; D012130:Respiratory Hypersensitivity / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012636:Secretory Rate / Q000187:drug effects
D008070:Lipopolysaccharides; C121546:ONO AE 248; C545650:PTGER4 protein, human; C545652:Ptger4 protein, rat; D012334:RNA, Neoplasm; D018078:Receptors, Prostaglandin E; D058309:Receptors, Prostaglandin E, EP4 Subtype; D015232:Dinoprostone