Cytokine responsiveness in cultured human small airway epithelial cells in relation to lung transplantation

We report a new method for collecting and establishing small airway epithelial cells (SAEC). This method enables the evaluation of the cytokine responsiveness of SAEC, which is still unknown. In this study we evaluated intercellular adhesion molecule-1 (ICAM-1) expression on SAEC stimulated with several inflammatory cytokines and compared it with that on large airway epithelial cells (LAEC). LAEC and SAEC were treated with IFN-gamma, TNF-alpha, IL-1beta, or their combination. ICAM-1 expression under various conditions was quantified by flow cytometry. Furthermore, immunocytochemical staining was performed to determine intranuclear displacement of signal transducer and activator transcription 1 (Stat1) during ICAM-1 expression by various cytokine stimulations. 1) ICAM-1 expression on both LAEC and SAEC was significantly increased by IFN-gamma stimulation alone and synergistically enhanced by IFN-gamma plus TNF-alpha or IL-1beta stimulation, 2) intranuclear displacement of Stat1 in SAEC by the stimulation with IFN-gamma plus TNF-alpha or IL-1beta was recognized earlier in comparison with that by IFN-gamma stimulation alone. The previously unknown peripheral cytokine responsiveness and its mechanisms of SAEC were revealed by this study, which contributes to the understanding of chronic lung allograft rejection recognized around small airways.