| Pulmonary Infection is one of the major health problems in our country,which has caused huge economic burden to the society.At the same time,with the emergence of resistant bacteria,the antibiotic treatment-oriented scheme is facing increasing challenges.Therefore,the study of body's anti-infection mechanism,it will be possible for us offers new ideas for treatment of pulmonary Infection.Macrophage is a highly heterogeneous immune cells,which is characterized by phenotypic plasticity and functional diversity.Under the stimulation of LPS or IFN-y and so on,macropage can be transformed into classifical activated macropages,which exhibit a variety of proinflammatory cytokines,such as TNF-,IL-6,IFN-y,iNOS and NO.It plays a role in killing bacteria,resisting pathogenic microorganism and Inhibiting tumor growth.M2 macrophages are polarized by Th2 cytokines such as IL-4 and IL-13,Which is characterized by the secretion of anti-inflammatory cytokines,such as IL-4,IL-10,IL-13,TGF-?.And It plays a role in tissue repair and reconstruction,lipid metabolism,allergic reactions and tumor growth.MRP8 and MRP 14,As a member of the danger-associated molecular patterns(DAMPs),often exist in the form of complexes.When the body is infected or damaged,neutrophils and macrophages release a large amount of MRP8/14,it is involved in the regulation of inflammatory and immune responses,and thus affect the pathophysiology of inflammation and infectious diseases.purpose:To investigate whether MRP8/14 can promote the transformation of macrophages into Ml macrophages and enhance its bactericidal ability.It also discusses whether MRP8/14 regulates the transformation of macrophages into Ml by activating NF-?B.The role of RAGE and TLR4 receptors in MRP8/14 regulation of macrophage polarization was examined by using knockout mice to further elucidate the mechanism by which MRP8/14 promoted the transformation of macrophages into Ml and enhanced their bactericidal abilitymethod:1 the changes of macrophages polarization induced by MRP8/14The expression of representative markers of macropage polarization were detected by flow cytometry,liquid phase chip and real-time fluorescence quantitative PCR respectively.2 Identification of Pathway of macropage polarization induced by MRP8/14.2.1 The phosphorylation of JNK,STAT1 and the activation of NF-?B signaling pathway induced by MRP8/14 were detected by Western blot.2.2 Raw264.7 cells were pretreated with The pathway specific inhibitor SP600125 and Bay11-7082 prior to MRP8/14 exposure.After MRP8/14 challenge,The expression representative makers were detected by Liquid chip,Real-time quantitative PCR and Flow cytometry respectively..3 The role of RAGE and TLR4 receptors in MRP8/14-regulated macrophage polarization was detected by knockdown miceResult:1.MRP8/14 promotes macrophage polarized to M1 phenotype.1.1 Experimental results showed that MRP8/14 could significantly upregulate the expression of Ml macrophages representative foctor(p<0.01)..2 MRP8/14 promotes M1 macropage polarization by activation of NF-?B pathway.2.1 Westerntem blot showed that MRP8/14 activates NF-?B and JNK pathway in Raw264.7 cells and has no effect on STAT1 pathway.The experimental results show that MRP8/14 can activate NF-?B and JNK signal transduction pathway in macropage.2.2 Raw264.7 cells were pretreated with The pathway specific inhibitor SP600125 and Bayl 1-7082 prior to MRP8/14 exposure.After MRP8/14(1.5 ug/ml)challenge for 6 hours.compared with MRP8/14 group,Expremental results showed that Bayll-7082+MRP8/14 group significantly reduced the expression of M1 marks(P<0.05),The results showed that MRP8/14 promotes M1 macropage polarization association with the activation of NF-?B signal pathway.3 TLR4 receptors are involved in the regulation of MRP8/14 on macrophages polarization.4 MRP8/14 can enhance the bactericidal ability of macrophagesConclusion:.MRP8/14 promotes the macrophages polarization into M1 by the activation of TLR-4-NF-?B pathway to enhance its bactericidal ability. |
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