Anti-inflammatory effect of adenovirus-mediated IκBα overexpression in respiratory epithelial cells

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Abstract
Many studies into basic biological characteristics of inflammation and tissue injury have implicated pro-inflammatory cytokine-mediated tissue injury in the pathogenesis of inflammatory lung diseases. Because transcription of most pro-inflammatory cytokines is dependent on the activation of nuclear factor (NF)-κB, NF-κB could be a good potential target to suppress the cytokine cascade. Cytokine-induced activation of NF-κB requires phosphorylation and subsequent degradation of IκBa. Therefore, the blocking NF-κB activation by IκBα could inhibit the pro-inflammatory cytokine-induced tissue injury. To evaluate whether blocking of NF-κB activation shows an anti-inflammatory effect, this study investigated the effect of adenovirus-mediated overexpression of IκBα super-repressor (IκBα-SR) on the pro-inflammatory cytokine expression in respiratory epithelial cells. The transduction efficiency of adenovirus was >90% in both A549 and NCI-H157 cells. Ad5IκBα-SR-transduced cells expressed high levels of IκBα-SR, which was resistant to tumour necrosis factor (TNF)-;α-;induced degradation. Adenovirus-mediated overexpression of IκBα-SR blocked cytokine-induced nuclear translocation of p65 and NF-κB deoxyribonucleic acid binding activity without affecting total cellular expression level of NF-κB. Ad5IκBα-SR transduction suppressed cytokine-induced interleukin-;8 and TNF-;α expressions at both ribonucleic acid and protein levels. These results suggest that blocking the nuclear factor-κB pathway by adenovirus-mediated overexpression of IκBα-super-repressor shows an effective anti-inflammatory effect in respiratory epithelial cells.