The Protective Effect of Low Dose of Lipopolysaccharide Pretreatment on Endotoxin-Induced Uveitis in Rats Is Associated with Downregulation of CSF-1 and Upregulation of LRR-1.

Yunli Ling,Shuo Yu,Jing Wang,Hong Lu,Wenjie Li

doi:10.1155/2020/9314756

Abstract

Purpose To observe the effect of low dose of lipopolysaccharide (LPS) pretreatment on the expression of CSF-1 and LRR-1 in rats with endotoxin-induced uveitis (EIU), and to explore the possible role of TLR4. Method EIU was induced by a single subcutaneous injection of 200 μg LPS. For the endotoxin tolerance group, the induction of EIU was preceded by a daily subcutaneous injection of 0.1 mg/kg LPS for five days. Clinical scores were graded at 24 h after EIU under a slit lamp microscope. HE stain was performed to observe the histopathology. The concentrations of IL-17, INF-γ, and IL-6 in aqueous humor were quantified with enzyme-linked immunosorbent assay. Real-time PCR, Western blot, and immunofluorescence analysis were used to determine the expression of NF-κB P65 and the activation of CSF-1, LRR-1. Results: Low dose of LPS pretreatment produced a suppressive effect by significantly reducing the inflammatory reaction of anterior segment as measured by slit lamp and histopathology. It also significantly reduced the concentrations of IL-17, INF-γ, and IL-6 in aqueous humor and the expression of CSF-1 and NF-κB P65, while increased the expression of LRR-1 compared to the EIU group. Conclusions Low dose of LPS pretreatment can ameliorate endotoxin-induced uveitis in rats. This protection may be associated with upregulation of LRR-1 and downregulation of CSF-1, which is regulated by TLR4 signaling pathway.

Highlights

Uveitis represents a group of conditions characterised by intraocular inflammation
Chen et al found that the levels of IL-17a, INF-γ, and IL-6 in aqueous humor were correlated with the activity of acute anterior uveitis [21]
Repeated injection of endotoxin resulted in the systemic release of IL-6, no IL-6 was detected in aqueous humor and no uveitis was found [15]

Summary

Introduction

Uveitis represents a group of conditions characterised by intraocular inflammation. The term uveitis includes iritis, cyclitis, and choroiditis; it encompasses inflammation of adjacent intraocular structures such as the retina, vitreous, and optic nerve [1]. Endotoxin-induced uveitis (EIU) is an efficient animal model to study pathological mechanisms associated with the disease [2]. It is mainly manifested as signs of acute anterior uveitis, such as ciliary congestion, iris blood vessels dilatation, anterior chamber exudate, pupil occlusion, and fibrous membrane formation. The activation of NF-κB P65 mediated by TLR4 signaling pathway is the key of acute anterior uveitis [5]

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Results

Conclusion