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

<jats:p><jats:italic>Purpose</jats:italic>. 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. <jats:italic>Method</jats:italic>. EIU was induced by a single subcutaneous injection of 200 <jats:italic>μ</jats:italic>g 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-<jats:italic>γ</jats:italic>, 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-<jats:italic>κ</jats:italic>B P65 and the activation of CSF-1, LRR-1. <jats:italic>Results</jats:italic>: 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-<jats:italic>γ</jats:italic>, and IL-6 in aqueous humor and the expression of CSF-1 and NF-<jats:italic>κ</jats:italic>B P65, while increased the expression of LRR-1 compared to the EIU group. <jats:italic>Conclusions</jats:italic>. 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.</jats:p>

CSF1/CSF1R-mediated Crosstalk Between Choroidal Vascular Endothelial Cells and Macrophages Promotes Choroidal Neovascularization

“…These results suggested that the CSF1/CSF1R axis played a vital role in the pathogenesis of nAMD. A previous study revealed that CSF1 was increased in the iris ciliary body of a rat endotoxin-induced uveitis model, and low-dose lipopolysaccharide pretreatment reduced the expression of CSF1, 29 which indicated that CSF1 acted as an inflammatory cytokine in endotoxin-induced uveitis.…”

Microglial Dynamics Modulate Vestibular Compensation in a Rodent Model of Vestibulopathy and Condition the Expression of Plasticity Mechanisms in the Deafferented Vestibular Nuclei

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“…LPS causes several mediators of inflammation to be released, including chemokines and pro-inflammatory cytokines, which ultimately cause cellular damage. 2,3 Toll-like receptor-4 (TLR-4) activated by LPS is known to stimulate Nuclear factor-κB (NFkB) and inhibitor of NF-κB kinase (IKK). Under unstressed conditions, NFkB resides in the cytoplasm together with an inhibitory factor (IκB).…”

“…LPS causes several mediators of inflammation to be released, including chemokines and pro-inflammatory cytokines, which ultimately cause cellular damage. 2,3…”