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H. Mashimo, N. Ohguro, Y. Tano; Gene Expression Changes During Lipopolysaccharide Tolerance in Endotoxin Induced Uveitis Rat Model. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2638.
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It has been well known that second challenge of lipopolysaccharide (LPS) could not induce the next ocular inflammation in endotoxin induced uveitis (EIU) in rats (LPS tolerance). The purpose of this study is to investigate further details about this phenomenon and to determine the cytokines which play a pivotal role in LPS tolerance.
EIU was induced in male Lewis rat by a single subcutaneous injection of 1mg/kg LPS at footpad. Rats treated with the same volume of saline solution were served as controls. 1, 3, 7, 14, 28, 56 or 72 days after EIU induction, second challenge of LPS was performed to EIU induced rats. On the same day, first challenge of LPS was done to control rats. 24 hours after each challenge, number of infiltrating cells and protein concentration in the aqueous humor were examined in both groups. Using real-time PCR technique, gene expression changes of inflammatory cytokines and toll-like receptor associated proteins (TNF-α, IL-6, IL-1ß, TGF-ß, IL-10, TLR4, MyD88, SOCS1, SHIP) in EIU induced rats were evaluated by comparing the mRNA level of these genes with those in control rats.
LPS tolerance apparently continued from day1 to day 56. On day 72, both EIU induced rats and control rats did not show ocular inflammation. On the other hand, mRNA levels of all investigated genes in tolerance induced rats significantly increased compared to those in control rats on day 1. On day 3, IL-1ß, IL-10, TLR4, MyD88 and SHIP still showed significant high levels of gene expression. On day 7; however, only IL-10 kept high expression level , which continued up to day 72.
This study suggested that IL-10 is one of the essential players in LPS tolerance of EIU in rats.
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