The Effect of Cytokine-Stimulation and Pharmacologic Intervention on PGE2 Production in Primary Human Conjunctival and Corneal Cells

ABSTRACT

We studied the production of PGE2 by human conjunctival and corneal cells in response to inflammation, and reduction of inflammation with non-steroidal anti-inflammatory drugs. Primary cultures of human conjunctival epithelial cells, fibroblasts, corneal epithelial cells, and keratocytes were incubated with IL-4 and TNF-α. PGE2 and COX-2 levels were analyzed. Effects of anti-inflammatory and anti-immune drugs on PGE2 production were also investigated. IL-4 and TNF-α induced the generation of PGE2 and COX-2 in conjunctival and corneal cells. Epithelial PGE2 production was significantly lower than in keratocytes and fibroblasts, which was down-regulated by aspirin. IL-4 and TNF-α enhanced the inflammatory response via prostaglandin production which contributed to ocular surface inflammation. Prostaglandin production was higher in stromal cells than epithelial cells. These results suggest that the epithelial barrier disruption may contribute to ocular allergic inflammation by the PGE2 production from stromal cells. Moreover, NSAIDs were effective in suppressing PGE2 production in our experiment.

Keywords:

• Allergic conjunctivitis
• cyclooxygenase
• cyclosporine A
• FK-506
• NSAID

Acknowledgments

We thank Ayako Igarashi for her skillful technical assistance.

Author contribution

ES, HY, and HF designed research, analyzed data and wrote the paper. HY, YS, KF, AN, DM, and NO performed research and research discussions.

Disclosure of interest

The authors report no conflicts of interest disclose.

Financial Disclosures

H. Fujishima has received grants from Alcon Laboratories, White Medical Co., Santen Pharmaceutical Co. Ltd, Senju Pharmaceutical Co. Ltd, and Otsuka Pharmaceutical Co. Ltd; and has consultant arrangements with Kobayashi Pharmaceutical Co. Ltd.

All authors read and approved the final manuscript.