Inhibitor of Apoptosis Protein Antagonists (IAP)- Birinapant shows anti-inflammatory and antioxidant effects on LPS stimulated human conjunctival epithelial cells.

Abstract

Purpose : (IAP) proteins are involved in various cell functions, including cell survival and protection from cell death. Some cell survival effects are mediated through activation of nuclear factor κB (NFκB) which is a central transcription factor involved in the production of pro-inflammatory cytokines and chemokines. SMAC-mimetics are small-molecule inhibitors of IAPs that mimic the endogenous SMAC. The aim of this pilot study was to investigate if the Smac mimetic Birinapant influences the inflammatory and oxidative stress response of human conjunctival epithelial cells (HCEjs) stimulated by LPS.

Methods : HCjEs were cultured in DMEM medium with 10% FBS for 24 hours containing 25 ng/ml LPS, before being subjected to Birinapant (0,52 mikroM) for an additional 24 hours. ROS production was then measured using immunofluorescent dye DCF. Further, using modified cell ELISA ICAM-1 surface expression was examined.

Results : LPS (25 ng/ml) induced a significant increase in ROS and ICAM-1 levels in the conjunctival epithelial cells (HCjE). The following addition of Birinapant not only inhibited the ROS productionbut also reduced ICAM-1 surface expression significantly.

Conclusions : Birinapant inhibition of icam-1 and ROS production was close to basal levels despite concomitant LPS stimulation. Birinapant did not increase cell death of HCEjs at the concentration applied. As Smac mimetics are being developed for clinical use as anti-cancer and anti-infective agents and seem to be well-tolerated, Smac mimetics might potentially be further evaluated for topical use as novel treatment for ocular surface diseases.

This is a 2020 ARVO Annual Meeting abstract.