The Equilibrium State Of STLR2/TLR2and The Negative Regulating Action In G~+Sepsis

ObjectiveThe morbidity and fatality of the sepsis is rising year by year.Sepsisi is the severe disease that threaten our health.Sepsis is very common disease in intensive care unit(ICU).But the treatment of sepsis is still not have some breakthrough.Sepsis is the severe result of the inappropriate inflammation.The TLR family plays a pivotal role in the prompt and efficient innate immune recognition of and response to an array of microorganisms and their components. LTA,which is the component of the G+bacterium, is triggering the inflammation via TLR2.it isbelieve that sTLR2is served as a critical first-line regulator of TLR2-mediated responses.Appropriate immune response is that the TLR-mediated release of some inflammation molecules and the endogenous TLR-signaling inhibitory mechanisms should keep balance.When sepsisi occur the condition of sTLR2/TLR2need to be researched.This experiment is used of cell stimulated by LTA in vitro.We want to research the condition of sTLR2/TLR2.We can explore some methods at basis of the regulator mechanism.So we may discover the therapeutics to control the inflammation and prevent the development of sepsis.MethodWe divided the U937cell into blank compare group,low-dose LTA group,middle-dose LTA group,high-dose LTA group,extreme-dose LTA group.After cultivated to corresponding time,we detection the sTLR、IL-10and IL-8by Elisa,the TLR2mRNA by PCR, the NF-kb translocation to nuclei by laser scanning confocal microscope(LSCM).Result1. The fluorescence intensities of NF-kb p65is the lowest in the blank control group,and the cell treated with the10ug/ml LTA group showed lower fluorescence intensities of NF-kb p65compared to the30ug/ml group.2. with The dose of LTA,wich come from staphylococcus aureus is changed,the secretion of sTLR2、IL-10and IL-8varyed.the sTLR2rised and the inflammation was controled in Low-dosed group and middle-dosed group by time, the sTLR2rised by time,the IL-8and TLR2mRNA rised sharply.the inflammation is very intensive.ConclusionLTA,which is the component of the G+bacterium, is triggering the inflammation via TLR2.Then the NF-kb pathway was activated. Immunofluorescence method was adopted to examine the expression of NF-kb subunit p65. the sTLR2and IL-10rised by time.the inflammation response was controled in Low-dosed group and middle-dosed group by time. bescause of the sTLR2,the inflammation response could be regulated. sTLR2a critical first-line regulator of TLR2-mediated responses.The change of TLR2mRNA in nucleus was opposited to the variation of the sTLR2.the sTLR2originates from an intracellular processing TLR2that does not require protein synthesis.Maybe the synthetize mechanism of sTLR2,so the opposite phenomenon happen.We should explore some methods according with the capacity of the sTLR2, we may discover the therapeutics to control the inflammation and prevent the development of sepsis.