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

Purpose: 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-M

Results: 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.

Keywords:

• Endotoxin-induced uveitis
• endotoxin tolerance
• IRAK-M
• LPS
• TLR-signaling pathway

DECLARATION OF INTEREST

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Funding

This study was supported by the National Nature Science Fund of China (81471575 and 81273246).

Additional information

Funding

This study was supported by the National Nature Science Fund of China (81471575 and 81273246).