719 The effect and irritation of adapalene on Cutibacterium acnes via HTS

Abstract

Cutibacterium acnes is involved in acne as an opportunistic pathogen. Contrary to the previously thought, the proliferation of C. acnes is not pathogenic crucially. Instead, activation of the innate immunity induced by C. acnes might lead to this chronic inflammation. This research was to establish the screening platform of acne by nematodes and detect the anti-inflammatory activity and stimulation of adapalene. High throughput liquid screening assay was developed here to identify effective anti-infective compounds in 96-well assay plates of worms. Tetracycline was as the positive control to save infected worms in the liquid assay. Minimum inhibitory concentration was presented for visible growth of C. acnes in different conditions. The membrane permeability of C. acnes was detected by monitoring the uptake of SYTOX Green after treating with compounds. We provided results from HTS in nematodes Caenorhabditis elegans that led to the better characterization of adapalene treating acne. Compared to tetracycline, adarotene inhibited the growth of C. acnes significantly (p<0.01), while adapalene didn’t show anti-C. acnes effect, even under high concentration. Then we found that adapalene reduced the production of pro-inflammatory cytokines (IL-6, IL-8) on PMA stimulated human epidermoid carcinoma cells. But when exposure of human keratinocytes to adapalene, it resulted in the activation of the cells and the secretion of IL-6 and IL-8. The liquid C. elegans - C. acnes assay established here allows screening for anti-acne compounds that are not toxic to hosts. We confirm the utility of C. elegans as a screening platform for acne treatment, and adapalene can rescue C. acnes infected worms. Although it has anti-inflammation effects, adapalene changes the expression of IL-6 and IL-8 depending on the host inflammation conditions. Normal human keratinocytes could be triggered by the stimulation of adapalene.