Inhibition of Zymosan-Induced Inflammatory Factors Expression by ATRA Nanostructured Lipid Carriers.

Hongyan Zhou,Xunyi Gao,Wensong Zhang,Hongguang Zhang,Ning Kong

doi:10.1155/2016/4952340

Abstract

Purpose. The study aimed to evaluate the effect of all-trans retinoic acid-loaded nanostructured lipid carriers (ATRA-NLCs) on the zymosan-induced expression of the cytokines IL-4, IL-10, and IFN-γ and the matrix metalloproteinases/tissue inhibitor of metalloproteinases (MMPs/TIMPs) and TLR2 in rabbit corneal fibroblasts (RCFs). Methods. ATRA-NLCs were prepared by emulsification. RCFs were isolated and harvested after four to seven passages in monolayer culture. Cytokine release (IL-4, IL-10, and IFN-γ) induced by zymosan was analyzed by cytokine release assay, reverse transcription, and real-time polymerase chain reaction (RT-PCR) analysis detection. MMP-1, MMP-3, and MMP-13, TIMP-1 and TIMP-2, and TLR2 expression were analyzed by immunoblotting. Results. ATRA-NLCs were resistant to light and physically stable, and the average size of the ATRA-NLCs was 200 nm. ATRA-NLCs increased the zymosan-induced release of IL-4 and IL-10 and decreased the release of IFN-γ by RCFs. ATRA-NLCs decreased the levels of TLR2 and MMPs/TIMPs above. Conclusions. ATRA may be a potent anti-inflammatory agent for the therapy of fungal keratitis (FK).

Highlights

Fungal keratitis (FK) is an ulcerative and sight-threatening infection of the cornea that sometimes leads to blindness
Because ATRA exhibits anti-inflammatory activity [10], we investigated the effect of ATRA-NLCs on the zymosaninduced expression of TLR2, IL-4, IL-10, and IFN-γ, as well as the function of matrix metalloproteinases (MMPs)/tissue inhibitor of metalloproteinase (TIMP) in rabbit corneal fibroblasts (RCFs)
The effects of ATRA-NLC at various concentrations (0, 0.01, and 0.1 μmol/mL) on the release of IL-4, IL-10, and IFN-γ induced by zymosan from RCFs were investigated first (Figures 2(a), 2(b), and 2(c))

Summary

Introduction

Fungal keratitis (FK) is an ulcerative and sight-threatening infection of the cornea that sometimes leads to blindness. Patients with FK have been treated with antifungal drugs that prevent the progression of corneal pathogenesis, further study is still needed. The objectives of this study were to investigate the effect of ATRA-NLC on the zymosaninduced expression of the cytokines IL-4, IL-10, IFN-γ, MMPs/TIMPs, and TLR2. A β-glucan component of the yeast cell wall, is a ligand of TLR2 and dectin-1 which stimulates macrophages to produce proinflammatory mediators [1]. Zymosan can regulate TLR2 gene expression in the context of neuroinflammation [2]. Fungal inflammation is mediated by the expression of TLR2 activation. TLRs may activate the innate immune system. TLRs have been used as a legitimate therapeutic strategy. Zymosan-induced TLR2 expression was investigated in this study

Objectives

Methods

Results

Conclusion