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.

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.