title: Prostaglandin E2 suppresses polyinosine-polycytidylic acid (polyI:C)-stimulated cytokine production via prostaglandin E2 receptor (EP) 2 and 3 in human conjunctival epithelial cells.
abstract: BACKGROUND
  Prostaglandin (PG) E(2) is produced during inflammatory responses and suppresses the production of cytokines induced by lipopolysaccharide stimulation in macrophages and dendritic cells. In this study, we examined the expression of PGE(2) receptors in human conjunctival epithelial cells and investigated whether PGE(2) downregulates polyinosine-polycytidylic acid (polyI:C)-induced cytokine production.
  
  
  METHODS
  ELISA and quantitative reverse transcription (RT)-PCR were used to examine the effects of PGE(2) on the polyI:C-induced cytokine expressions by primary human conjunctival epithelial cells (PHCjEC). Reverse transcription-PCR was performed to examine the mRNA expression of the PGE(2) receptors EP1, -2, -3 and -4.
  
  
  RESULTS
  PGE(2) significantly attenuated the expressions of chemokine (C-C) motif ligand (CCL) 5, chemokine (C-X-C motif) ligand (CXCL) 10, CXCL11 and interleukin (IL) 6 in PHCjECs. Human conjunctival epithelial cells exhibited expression of EP2, -3 and -4, but not of EP1. EP2 agonist significantly suppressed the polyI:C-induced the expressions of CCL5, CXCL10 and CXCL11 but not of IL-6. EP3 agonist significantly suppressed the expressions of CCL5, CXCL10, CXCL11 and IL-6. On the other hand, EP4 agonist failed to suppress the cytokine production induced by polyI:C stimulation.
  
  
  CONCLUSIONS
  Our results show that PGE(2) attenuated the expression of CCL5, CXCL10 and CXCL11 via both EP2 and EP3, and that the expression of IL-6 was attenuated only by EP3.
authors.affiliation: Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan. mueta@koto.kpu-m.ac.jp
authors.forename: Mayumi
authors.initials: M
authors.lastname: Ueta
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Matsuoka
authors.forename: Norihiko
authors.initials: N
authors.lastname: Yokoi
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kinoshita
mesh_terms: D003228:Conjunctiva / Q000187:drug effects / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D015232:Dinoprostone / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D011070:Poly I-C / Q000378:metabolism*; D018078:Receptors, Prostaglandin E / Q000819:agonists / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016207:Cytokines; D018078:Receptors, Prostaglandin E; D000242:Cyclic AMP; D015232:Dinoprostone; D011070:Poly I-C