Effect of endotoxin tolerance on nucleotide-binding oligomerization domain containing 2 signaling pathway
ZHANG Huijun1, WANG Baoqing1, QU Jieming2
1. Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China; 2. Department of Pulmonary Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
Abstract：To investigate the potential effect of endotoxin tolerance on nucleotide-binding oligomerization domain containing 2 (NOD2) signaling pathway, murine macrophage RAW264.7 cells were pretreated with lipopolysaccharide (LPS, 100 ng/mL) or phosphate buffered saline (PBS) for 20 h to establish endotoxin tolerance group and control group respectively. Both groups were subjected to the treatment with LPS (1 000 ng/mL) or heatkilled Aspergillus fumigatus (HAf). The mRNA levels of NOD2, receptor-interacting protein 2 (RIP2) and tumor necrosis factor α (TNF-α) were measured at 0, 2, 6, 12, 24 h after stimulation by real-time quantitative polymerase chain reaction (PCR). The concentrations of secreted TNF-α and interleukin 8 (IL-8) were also quantified by enzyme-linked immunosorbent assay (ELISA). The collective results showed that neither LPS nor HAf had any significant effect on NOD2, RIP2, and TNF-α transcription or TNF-α and IL-8 secretion in the endotoxin tolerance group. On the contrary, a clear up-regulation was detected in the control group upon either LPS or HAf treatment, concomitant with a peak at 12 h after stimulation. These data indicate that the NOD2 signaling pathway might be suppressed under endotoxin tolerance conditions.
2016, Vol. 11 
