Expression And Significance Of ST2 Receptor On Monocytes In Sepsis Mice

Objective Sepsis is the result of an imbalance between the inflammatory response syndrome and the compensatory inflammatory response syndrome.Monocytes,as the important inflammatory cells,play a critical role in the sepsis and participate the occurrence and development of sepsis,therefore,reducing the release of inflammatory factors by monocytes will help to alleviate the inflammatory response to sepsis.A series of studies have confirmed that the IL-33 / ST2 signal pathway is related to sepsis,it can reduce the body’s inflammatory response by block this pathway.The purpose of this project is to study the expression of ST2 receptors on monocytes in sepsis mouse,to research the relationship between IL-33 / ST2 and monocytes,and to explore the effects of ST2 on inflammatory factors released by sepsis monocytes.Methods(1)Preparation of animal models: The mouse cecal ligation and puncture(CLP)model was used to be established and evaluated;The peripheral blood and lung organs were obtained from mouse of different groups.(2)HE staining was performed on the lung tissue of each group of mouse,and then to evaluate the pathological changes;Immunohistochemical analysis was performed to quantitatively determine the interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in the lung tissue of model mice,(3)The peripheral blood of each group of mouse was collected for flow cytometry to detect the changes of monocytes numbers,inflammatory factor levels,and the expression of ST2 receptors on the surface of monocytes.(4)Monocytes were isolated from peripheral blood of 24 h group of sepsis mouse and cultured in vitro,the ST2 receptor on the surface of monocytes was blocked to observe its effect on the release of inflammatory factors by monocytes.Results(1)A cecal ligation and puncture sepsis mouse model was successfully established.(2)The results of HE staining of mouse lung tissue showed that the pathological changes of lung tissue in the CLP group were progressively aggravated over time compared with the sham group.The immunohistochemical results showed that the average optical density value of IL-6 in the CLP group was significantly higher than the sham group(p <0.01),and reached the highest peak at 12 h,the average optical density of TNF-α in the 24 h group was higher than the sham group,the 6h group,and the 48 h group(p<0.05).(3)The numbers of monocytes and the concentrations of IL-33,IL-1β,IL-12,and IL-27 in the CLP group were higher than the sham group,and all showed a trend of first increase and then decrease;The percentage of ST2 positive monocytes in the CLP group was higher than that of the sham group(p<0.05),and reached the highest peak at 24 h.(4)The concentration of IL-1β in the culture supernatant of monocytes was significantly lower in the ST2 receptor blocker group(p<0.01),and the IL-12 concentration was lower in the ST2 receptor blocker group(p<0.05),but there was no significant difference in the concentration of IL-27 between the two groups(p>0.05).Conclusion The expression of ST2 receptors on the surface of monocytes increased at first and then decreased with the course of disease.Blocking ST2 receptors can reduce the release of inflammatory factors by monocytes.