Decrease in toll-like receptors 2 and 4 in the spleen of mouse with endotoxic tolerance

Objective: Down-regulation of toll-like receptor (TLRs) is present in animals with endotoxin tolerance. The spleen is the largest peripheral lymphatic organ in vivo, and it plays an important role in inflammatory reactivity. In this study we investigated TLR2 and TLR4 proteins in the spleen of endotoxic tolerant mice. Methods: The TLR2 and TLR4 proteins were quantitatively detected by Western blotting, and their locations in the spleen were observed by immunohistochemistry. IL1-beta mRNA in the spleen was analyzed by real-time quantitative PCR. Results: The mice pretreated with 0.5 mg/kg/day of LPS for 14 days exhibited a decrease of TLR2 and TLR4, and presented endotoxin tolerance. In addition, a bolus injection of 10mg/kg LPS for mice with endotoxic tolerance caused no alteration of TLR2 and TLR4 proteins and no change of IL1-beta mRNA expression in the spleen. Conclusion: TLR4 is the target of endotoxic tolerance induction. The induction of cross-tolerance of TLR2 following LPS challenge is present in vivo with endotoxin tolerance.