摘要
Background Azithromycin can reduce neutrophil accumulation in neutrophilic pulmonary diseases.However,the precise mechanism behind this action remains unknown.Our experiment assessed whether azithromycin inhibits neutrophil accumulation in the airways by affecting interleukin-17 （IL-17） downstream signals.Methods Mice were pretreated with azithromycin before murine IL-17A （mlL-17） stimulation.After the mlL-17 stimulation,the levels of six neutrophil-mobilizing cytokines were determined by enzyme-linked immunosorbent assay （ELISA） tests in bronchoalveolar lavage （BAL） fluid; IL-6,CXC chemokine ligand-1 （CXCL-1）,CXCL-5,macrophage inflammatory protein-2 （MIP-2）,granulocyte colony-stimulating factor （G-CSF）,and granulocyte macrophage colony-stimulating factor （GM-CSF）.The number of neutrophils in BAL fluid were evaluated by cytospin preparations.Results （1） Azithromycin pretreatment significantly inhibited both the release of three neutrophil-mobilizing cytokines （MIP-2,CXCL-5 and GM-CSF） and the accumulation of neutrophils in airways caused by mlL-17 stimulation.（2） The levels of three neutrophil-mobilizing cytokines （IL-6,MIP-2 and GM-CSF） were positively correlated with the numbers of neutrophil in BAL fluid.Conclusions Azithromycin can inhibit neutrophil accumulation in the airways by affecting IL-17 downstream signals.This finding suggests that macrolide antibiotic application might be useful in prevention of neutrophilic pulmonary diseases characterized by high levels of IL-17.
Background Azithromycin can reduce neutrophil accumulation in neutrophilic pulmonary diseases.However,the precise mechanism behind this action remains unknown.Our experiment assessed whether azithromycin inhibits neutrophil accumulation in the airways by affecting interleukin-17 （IL-17） downstream signals.Methods Mice were pretreated with azithromycin before murine IL-17A （mlL-17） stimulation.After the mlL-17 stimulation,the levels of six neutrophil-mobilizing cytokines were determined by enzyme-linked immunosorbent assay （ELISA） tests in bronchoalveolar lavage （BAL） fluid; IL-6,CXC chemokine ligand-1 （CXCL-1）,CXCL-5,macrophage inflammatory protein-2 （MIP-2）,granulocyte colony-stimulating factor （G-CSF）,and granulocyte macrophage colony-stimulating factor （GM-CSF）.The number of neutrophils in BAL fluid were evaluated by cytospin preparations.Results （1） Azithromycin pretreatment significantly inhibited both the release of three neutrophil-mobilizing cytokines （MIP-2,CXCL-5 and GM-CSF） and the accumulation of neutrophils in airways caused by mlL-17 stimulation.（2） The levels of three neutrophil-mobilizing cytokines （IL-6,MIP-2 and GM-CSF） were positively correlated with the numbers of neutrophil in BAL fluid.Conclusions Azithromycin can inhibit neutrophil accumulation in the airways by affecting IL-17 downstream signals.This finding suggests that macrolide antibiotic application might be useful in prevention of neutrophilic pulmonary diseases characterized by high levels of IL-17.
基金
This work was partly supported by a grant from National Science Foundation of China （No.30871122）.
