Objective: To investigate the changes in Toll-like receptor (TLR) 2 and 4 gene expression in vital organs in septic rats and their potential regulation mechanism.
Methods: One hundred Wistar rats were randomly divided into normal controls (n=10), sham-operated group (n=10), septic group (n=60), and recombinant bactericidal/permeability increasing protein (BPI)-treated group (n=20). Severe sepsis was replicated by cecal ligation and puncture (CLP). Animals were sacrificed at different time points after CLP, tissue TLR2/4 mRNA expression in the liver, lungs, kidneys as well as intestine were measured by reverse transcription-polymerase chain reaction (RT-PCR). Plasma levels of tumor necrosis factor-alpha(TNF-alpha) and interleukin-10 (IL-10) were also determined by enzyme linked immunoadsorbent assay (ELISA).
Results: TLR2/4 mRNA could be detected in various tissues with low values both in normal controls and sham-operated group, but they were markedly up-regulated at 2 hours after CLP, peaking at 6-12 hours. Tissue TLR4 mRNA was gradually down-regulated 24 hours later, while TLR2 mRNA levels maintained high values up to 72 hours. In comparison with the CLP group, treatment with BPI significantly decreased TLR2 mRNA in various tissues at 12 and 24 hours (P<0.05 or P<0.01), also tissue TLR4 mRNA at 12 hours (P<0.05 or P<0.01), without marked influence on TLR4 mRNA expression at 24 hours in liver, lungs and small intestine (P>0.05). In addition, treatment with BPI could significantly lower plasma TNF-alpha levels at 12 hours post-CLP, on the other hand markedly elevate plasma IL -10 levels 24 hours later (P<0.01).
Conclusion: These data suggest that severe peritoneal infection could result in up-regulation of TLR2/4 mRNA expression in vital organs, which might play important roles in mediating proinflammatory cytokine synthesis and release. Endotoxemia appears to be involved in the activation of tissue TLR2/4 expression associated with CLP-induced sepsis.