Effect of FK506 and cyclosporin A on Iκ Bα degradation and IKKα pathway in bronchial epithelial cells, monocytes, lymphocytes and alveolar macrophages

Abstract

Background: Cyclosporin A(CsA) and tacrolimus(FK506) have been widely used as immunosuppressants. The effects of CsA, or FK506, on the I κB/NF- κB pathway have been shown to vary according to the cell type. However, their effects on the I κKB/NF- κB pathway have not been reported in bronchial epithelial cells. In this study, the effects of CsA and FK506 on the I κB/NF- κB pathway in bronchial epithelial cells, monocytes, lymphocytes and alveolar macrophages were evaluated. The relationship between their effects on the I κB/NF- κB pathway and I κB kinase(IKK) activity was also investigated. Methods: 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-1 β. The I κB a expressions were assayed by Western blot analyses. The IKK activity was evaluated by an in vitro immune complex kinase assay, using GST-I κ B α a as the substrate. Results: Neither CsA nor FK506 affected the level of I κ B α expression in any of the cell types used in this study. CsA pre-treatment inhibited the TNF α-induced I κ B α degradation in bronchial epithelial cells. In contrast, the TNF α-induced I κ B α degradation was not affected by FK506 pre-treatment. However, FK-506 suppressed the cytokine-induced I κ B α degradation in the pulmonary alveolar macrophages, peripheral blood monocytes and lymphocytes. The inhibitory effect of CsA, or FK506, on I κ B α degradation was not related to IKK Conclusions: CsA and FK506 suppressed the I κ B α degradation in bronchial epithelial cells, monocytes, lymphocytes and alveolar macrophages, so this may not be mediated through IKK.