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Prostaglandin E2 suppresses polyinosine–polycytidylic acid (polyI:C)-stimulated cytokine production via prostaglandin E2 receptor (EP) 2 and 3 in human conjunctival epithelial cells
  1. Mayumi Ueta1,2,
  2. Toshiyuki Matsuoka3,
  3. Norihiko Yokoi1,
  4. Shigeru Kinoshita1
  1. 1Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan
  2. 2Research Center for Inflammation and Regenerative Medicine, Faculty of Life and Medical Sciences, Doshisha University, Kyoto, Japan
  3. 3Department of ophthalmology, Hyogo Prefectural Amagasaki Hospital, Hyogo, Japan
  1. Correspondence to Mayumi Ueta, Department of Ophthalmology, Kyoto Prefectural University of Medicine, 465 Kajiicho, Hirokoji, Kawaramachi, Kamigyoku, Kyoto 602-0841, Japan; mueta{at}


Background Prostaglandin (PG) E2 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 PGE2 receptors in human conjunctival epithelial cells and investigated whether PGE2 downregulates polyinosine–polycytidylic acid (polyI:C)-induced cytokine production.

Methods ELISA and quantitative reverse transcription (RT)-PCR were used to examine the effects of PGE2 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 PGE2 receptors EP1, -2, -3 and -4.

Results PGE2 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.

Conclusion Our results show that PGE2 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.

  • Prostaglandin E2 (PGE2)
  • human conjunctival epithelial cells
  • prostaglandin E receptor 3
  • prostaglandin E receptor 2
  • ocular surface
  • conjunctiva
  • inflammation
  • drugs
  • experimental and laboratory

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  • The work described in the present paper was carried out in collaboration with Ono Pharmaceutical Co., Ltd., who supplied ONO-AE-259, ONO-AE-248 and ONO-AE-329 used in this study.

  • Funding This work was supported in part by grants-in-aid for scientific research from the Japanese Ministry of Health, Labour and Welfare and the Japanese Ministry of Education, Culture, Sports, Science and Technology, and research grants from the Kyoto Foundation for the Promotion of Medical Science, the Intramural Research Fund of Kyoto Prefectural University of Medicine and the Shimizu Foundation.

  • Competing interests None to declare.

  • Patient consent Obtained.

  • Ethics approval This study was approved by the institutional review board at Kyoto Prefectural University of Medicine, Kyoto, Japan. All experimental procedures were conducted in accordance with the tenets of the Declaration of Helsinki.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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