Mechanism of systemic inflammatory response syndrome induced by EC DNA / 中国病理生理杂志

ABSTRACT

AIM: To investigate whether the bacterial DNA participates in SIRS and its possible mechanism. METHODS: Escherichia coli genomic DNA (EC DNA) was extracted and purified from Escherichia coli 25922 by alkaline lysis method. Mortality of mice challenged with EC DNA and the changes of TNF-? and IL-6 in rat serum were observed. ANA-1 cells were cultured in vitro, after the cells were stimulated by different concentrations of EC DNA and LPS, the level of TNF-? and IL-6 in supernatant were tested. Meanwhile,expression of TLR9 and TLR4 on cell surface was measured. Activation of NF-?B was also observed. RESULTS: The lethal effect of EC DNA on mice with an obvious dose-effect relationship was observed. The death happened within 24 hours. Calf thymus DNA and DNase I-treated EC DNA did not lead to mice to die. The changes of serum TNF-? and IL-6 in rats induced by EC DNA and LPS were similar, but TNF-? peak level of EC DNA group appeared 1 hour earlier than that of LPS group. In vitro, large amount of TNF-? and IL-6 were released from ANA-1 cells stimulated by EC DNA. High expression of TLR9 and TLR4 was observed on surfaces of THP-1 cells. In particularly, LPS induced strong activation of NF?B. The results suggested other pathway possibly took part in the signal transduction inducea by EC DNA. CONCLUSION: EC DNA has the abilities to lead to death of mice, and induces serum TNF-? and IL-6 level to increase in rats and ANA-1 cells to release cytokines in vitro. High expression of TLR9 and TLR4, strong activation of NF-?B may be its important molecular mechanism, but other pathway probably exists to play an important role.