Abstract
Purpose :
The aim of this study is to investigate the role of IL-1 receptor-associated kinase–M (IRAK-M) in regulating endotoxin tolerance (ET) in rat model of endotoxin-induced uveitis (EIU).
Methods :
Male Wistar rats were subcutaneous injected with 200μg lipopolysaccharide (ET group) or an equivalent volume of normal saline (EIU group and blank control group), and 24h later, subcutaneous injection of 200μg LPS (ET group and EIU group) or an equivalent volume of normal saline (blank control group) was carried out. The clinical manifestation was observed and scored at 2-h intervals using a slit microscope. The degree of inflammatory reaction was determined by routine histological examinations, and the expression of IRAK-M and NF-κb in the iris-ciliary body complex was detected through Real-time RT-PCR and Western blot analyses.
Results :
Endotoxin tolerance produced suppressive effects on inflammation by significantly reducing the clinical severity of EIU as well as fibrin exudations and inflammatory cell infiltration in the eye. Protein and mRNA levels of NF-κB was significantly suppressed in endotoxin tolerance group compared with in EIU group (p<0.05), while the expression of IRAK-M was remarkably elevated in endotoxin tolerance group (p<0.05).
Conclusions :
Endotoxin tolerance in rat model of endotoxin-induced uveitis blunts LPS-mediated activation of NF-κB. Furthermore, endotoxin tolerance increases expression of IRAK-M in rat iris-ciliary body, suggesting its involvement in reprogramming TLR4 signaling pathways that transduces expression of inflammatory mediators.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.