Interferences in myeloid NF-κB signaling affects the inflammatory phenotype after acute smoke exposure and worsens lung damage in a murine model of cigarette smoke-induced emphysema
Cigarette smoking is the main risk factor for the chronic obstructive pulmonary disease (COPD). It was the aim of this study to examine the function of myeloid cell nuclear factor-κB (NF-κB) in cigarette smoke (CS) induced lung inflammation and lung damage. We exposed wild type mice and mice deficient for myeloid RelA/p65 or myeloid IκBα to acute or chronic CS. Numbers of macrophages were increased in RelA/p65-deficient mice and decreased in IκBα-deficient mice after acute cigarette smoke exposure. In the chronic CS model, assessment of pulmonary function showed that the total lung capacity was increased in room air and CS exposed RelA/p65- and IκBα-deficient mice. The respiratory compliance and resistance was increased and the tissue elasticity was decreased in room air exposed IκBα-deficient mice. Histology and morphometry showed that chronic exposure to CS results in loss of lung structure in RelA/p65- and IκBα-deficient mice. In conclusion, myeloid NF-κB regulates the influx of macrophages into the lung in the acute smoke setting. Myeloid NF-κB is required for maintenance of pulmonary function and lung structure and its deregulation worsens CS-induced lung damage.