Cyclosporin A(CsA) and tacrolimus(FK506) have been widely used as immunosuppressants. The effects of CsA, or FK506, on the IκB/NF-κB pathway have been shown to vary according to the cell type. However, their effects on the IκB/NF-κB pathway have not been reported in bronchial epithelial cells. In this study, the effects of CsA and FK506 on the IκB/NF-κB pathway in bronchial epithelial cells, monocytes, lymphocytes and alveolar macrophages were evaluated. The relationship between their effects on the IκB/NF-κB pathway and IκB kinase(IKK) activity was also investigated.

BEAS-2B and A549 cells, pulmonary alveolar macrophages, peripheral blood monocytes and lymphocytes were used. The cells were pre-treated with CsA, or FK506, for various time periods, followed by stimulation with TNF-α, LPS or IL-1β. The IκBα expressions were assayed by Western blot analyses. The IKK activity was evaluated by an in vitro immune complex kinase assay, using GST-IκBα as the substrate.

Neither CsA nor FK506 affected the level of IκBα expression in any of the cell types used in this study. CsA pre-treatment inhibited the TNFα-induced IκBα degradation in bronchial epithelial cells. In contrast, the TNFα-induced IκBα degradation was not affected by FK506 pre-treatment. However, FK506 suppressed the cytokine-induced IκBα degradation in the pulmonary alveolar macrophages, peripheral blood monocytes and lymphocytes. The inhibitory effect of CsA, or FK506, on IκBα degradation was not related to IKK.

CsA and FK506 suppressed the IκBα degradation in bronchial epithelial cells, mono. cytes, lymphocytes and alveolar macrophages, so this may not be mediated through IKK.