Prostaglandin E2 Suppresses Poly I

Abstract

We previously reported that prostaglandin (PG) E2 acts as a ligand for prostaglandin E receptor 3 (EP3) in conjunctival epithelial cells, that it downregulates the progression of experimental murine allergic conjunctivitis, and that in human conjunctival epithelial cells it modulates the expression of polyI:C-induced proinflammatory genes via prostaglandin E receptor 2 (EP2) and EP3, suggesting that PGE2 might have important roles in ocular surface inflammation such as allergic conjunctivitis. Here, we investigated whether PGE2 also downregulates polyI:C-induced cytokine production in human corneal epithelial cells. We used enzyme-linked immunosorbent assay and quantitative reverse transcription-polymerase chain reaction to examine the effects of PGE2 on polyI:C-induced cytokine expression by immortalized human corneal-limbal epithelial cells (HCLE). Using reverse transcription-polymerase chain reaction, we examined the messenger RNA (mRNA) expression of the PGE2 receptor, EP1-4. PGE2 significantly attenuated the expression of CC chemokine ligand (CCL)5 (P < 0.0005), CCL20 (P < 0.0005), C-X-C chemokine (CXCL)10 (P < 0.0005), CXCL11 (P < 0.05), and interleukin (IL)-6 (P < 0.005) in human corneal-limbal epithelial cells. Human corneal epithelial cells manifested the mRNA expression of EP2, EP3, and EP4, but not EP1. The EP2 agonist significantly suppressed the polyI:C-induced expression of CCL5 (P < 0.005), CXCL10 (P < 0.0005), and CXCL11 (P < 0.05) but not of CCL20 and IL-6. The EP3 agonist significantly suppressed the expression of CCL5 (P < 0.05), CCL20 (P < 0.005), CXCL10 (P < 0.0005), CXCL11 (P < 0.0005), and IL-6 (P < 0.005). The EP4 agonist failed to suppress cytokine production induced by polyI:C stimulation. Our results show that in human corneal epithelial cells, PGE2 attenuated the mRNA expression and production of CCL5, CXCL10, and CXCL11 via both EP2 and EP3, and that the mRNA expression and production of CCL20 and IL-6 was attenuated only by EP3.