Resp Res
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To determine if nuclear factor-kappaB (NF-kappaB) activation may be a key factor in lung inflammation and respiratory dysfunction, we investigated whether NF-kappaB can be blocked by intratracheal administration of NF-kappaB decoy oligodeoxynucleotides (ODNs), and whether decoy ODN-mediated NF-kappaB inhibition can prevent smoke-induced lung inflammation, respiratory dysfunction, and improve pathological alteration in the small airways and lung parenchyma in the long-term smoke-induced mouse model system. We also detected changes in transcriptional factors. In vivo, the transfection efficiency of NF-kappaB decoy ODNs to alveolar macrophages in BALF was measured by fluorescein isothiocyanate (FITC)-labeled NF-kappaB decoy ODNs and flow cytometry post intratracheal ODN administration. ⋯ In contrast, these NF-kappaB decoy ODNs-treated mice showed significant increase in the level of tumor necrosis factor-alpha(TNF-alpha) and pro-MMP-9(pro-matrix metalloproteinase-9) in mice BALF. Further measurement revealed administration of NF-kappaB decoy ODNs did not prevent pathological changes. These findings indicate that NF-kappaB activation play an important role on the recruitment of macrophages and pulmonary dysfunction in smoke-induced chronic lung inflammation, and with the exception of NF-kappaB pathway, there might be complex mechanism governing molecular dynamics of pro-inflammatory cytokines expression and structural changes in small airways and pulmonary parenchyma in vivo.