Protection of Lipopolysaccharide (LPS) Preconditioning against Endotoxin-Induced Uveitis (EIU) in Rats is Associated with Overexpression of Interleukin-1 Receptor-Associated Kinase M (IRAK-M)

Abstract

ABSTRACTPurpose: To investigate the protective effect of LPS preconditioning against EIU in rats.Methods: EIU in Wistar rats was developed by subcutaneous injection of LPS (200 μg). Lower dose of LPS (0.1 mg/kg, intraperitoneally) or its carrier was injected daily for five days before EIU induction. Twenty-four hours after EIU, eyes were examined and then enucleated. The degree of inflammatory reaction was determined by routine histological examinations. Real-time RT-PCR and Western blot were used to determine the activation of NF-kB and expression of IRAK-1, IRAK-4, and IRAK-MResults: Repeated pre-administration of LPS induced a significant reduction in ocular inflammation and the expression of NF-κb p65 in neurons. The expression of IRAK-1 and IRAK-4 was suppressed in endotoxin tolerance group, whereas IRAK-M was increased.Conclusions: Endotoxin tolerance has a protective effect against EIU, and upregulation of IRAK-M through TLR-signaling pathway is one of the most likely candidates to be involved in the observed phenomenon.