Exposure to cigarette smoke upregulates AP-1 activity and induces TNF-alpha overexpression in mouse lungs.

Cigarette smoke-triggered inflammation is important in the pathophysiology of chronic obstructive pulmonary disease, and involves overexpression of many proinflammatory genes. Transcription factors regulating expression of inflammatory mediators may play a key role in characterizing the disease. To observe alterations in pulmonary function, observe pathological changes in lung tissues, and detect changes in transcriptional factors, mice were exposed to 30 days of cigarette smoke. Pulmonary function was measured by pressure sensors, and pathological changes were observed in lung tissue sections. Nuclear factor (NF)-kappaB and AP-1 activities were detected by electrophoretic mobility shift assay (EMSA). The levels of inflammatory mediators tumor necrosis factor (TNF)-alpha, interleukin(IL)-6, and IL-8 in bronchoalveolar lavage fluid (BALF) were measured using enzyme-linked immunosorbent assay (ELISA). Pulmonary function was not markedly decreased after 30 days of smoke exposure. Exposure to this regimen of cigarette smoke induced peribronchial and perivascular lymphocytic aggregates and parenchymal accumulation of macrophages in mice. EMSA demonstrated that smoke exposure enhanced activator protein (AP)-1 DNA binding activation, but only slightly changed NF-kappaB activation in mouse lung. Compared to the control group, smoke exposure induced a notable increase in TNF-alpha in BALF. These data demonstrated that subacute smoke-triggered lung inflammation was accompanied by inflammatory cell influx, AP-1 activation, and proinflammatory gene overexpression in mouse lungs.