The Mechanism Of Dexamethasone And N-acetyl-l-cysteine Inhibits Expression Of IL-8 And ICAM-1 In A549 Cells

Objective:To study the dexamethasone(DXM) and n-acetyl-1-cysteine(NAC) inhibition of human alveolar epithelial cells(A549) inflammatory factor, interleukin-8(IL-8) and intercellular adhesion moleculeol-1(ICAM-1) expression mechanism.Method:With the tumor necrosis factor alpha(TNF-α) and lipopolysaccharide(LPS), trichostatin A(TSA),DXM and NAC act on A549 cells respectively, with ELISA and flow cytometry method respectively detecting inflammation factor IL-8, the expression of ICAM-1; Western Boltting to detect protein of glucocorticoid receptor(GR), histone deacetylases 1 and histone deacetylases 2(HDAC1,2), a transcription factor activator protein-1(AP-1), and nuclear factor κB(NF-κB) expression and spectrophotometry to detect the activity of HDAC; Results:With TNF-α act on A549 cells before and after,compared the two groups of IL-8 protein concentration improved obciously, it was statistically significant difference(P<0.05). Compared with TNF-α role alone group, DXM and NAC preaction groups can obviously reduce the TNF-α induced the expression of IL-8,the difference was statistically significant(P<0.05). With TNF-α act on A549 cells before and after,compared the two groups of ICAM-1 protein concentration(fluorescence intensity) improved obciously, it was statistically significant difference(P<0.05). Compared with TNF-α role alone group, DXM and NAC can obviously reduce the TNF-α preaction cells induced the expression of ICAM-1, the difference was statistically significant(P<0.05). TNF-α, LPS induced A549 cells, AP-1, the NF-κB transcription activation; DXM obvious inhibition of transcription factors of AP-1 and NF-κB transcription activation. NAC significantly inhibit transcription factor NF-κB,have no effect with AP-1. TNF- α, LPS reduce the protein expression of HDAC1,2 in A549 cells, DXM significantly increased the protein expression of HDAC1,2 in A549 cells; NAC have no effect with the expression of HDAC1,2 in A549 cells. Compared with the groups of untreated,TNF-α and LPS significantly reduced activity of HDAC(P<0.05). Activity of HDAC after DXM and NAC effected, activity of HDAC significantly increased in DXM gourp(P<0.05), NAC have no effect with activity of HDAC(P>0.05).Conclusion:DXM, NAC can obviously antagonism expression of IL-8,ICAM-1 induced by TNF-α.They have strong anti-inflammatory effects. DXM mainly by increasing the HDAC protein expression and activity of HDAC,inhibition of transcription factors AP-1 and NF-κB transcription activation then play anti-inflammatory effects, NAC have no effect on expression of HDAC and activity of HDAC.Results of all tests prompt NAC is not through acetylation signal mechanism play the role of anti-inflammatory.