Biomedical Research

Fungal Keratitis (FK) is the main corneal infection that is resistant to antifugi drugs. Exploring new agent will be important for the drug resistance and new infectious diseases. All-Trans-Retinoic Acid (ATRA), a bioactive derivative of vitamin A, is immunoregulatary and anti-inflammation agent by decreasing the expression of the pro-inflammatory cytokines and increasing the expression of antiinflammatory factors. The study was to investigate the potential role of ATRA to be a supplementary method for the therapy of FK. The aim of this study was to investigate the role of ATRA Nanostructured Lipid Carriers (NLC) in the zymosan induced cytokines (IL-17, ICAM-1, MIP-2, MCP-1 and Ip-10) by Corneal Fibroblasts (CFs) and to investigate the characters of ATRA-NCL. ATRA-NLC was prepared by the method of Emulsification process from scratch. ATRA-NCL concentration was calculated by High Performance Liquid Chromatography (HPLC) method. ATRA-NCL physical stability was observed. ATRA-NCL Cytotoxicity assay was performed by the detection of Lactate Dehydrogenase (LDH). The role of ATRA-NCL on the release of IL-17, ICAM-1, MIP-2, MCP-1, IP-10 induced by zymosan was examined by ELISA. The relative NF-KB-p65, P-ERK1, 2, P-IκBα cell signal pathway was assayed by immune blot analysis. The mean diameter of ATRA-NLC was 200 nm. ATRA-NCL physical stability study showed well at 4°C without precipitation and crystallization. The NLC particles were dispersed well under the scanning electron microscope (S-4800). Scanning electron microscope image of the ATRA particles were shown. ATRA-NCL showed no cytotoxic effect on KCs. ATRA-NCL inhibited zymosan-induced IL-17, ICAM-1, MIP-2, MCP-1, Ip-10 release by CKs. ATRA-NCL inhibited NF-KBp65, P-ERK, P-IκBα signalling pathways induced by zymosan in KCs. ATRA-NLC can inhibit the releasing of cytokines (IL-17, ICAM-1, MIP-2, MCP-1, Ip-10) induced by zymosan in CFs. It was supplementary selection for the therapy of fungal keratitis.

Author(s): Hongyan Zhou, Xunyi Gao, Wensong Zhang, Hongguang Zhang, Ning Kong
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