Effect of FK506 and Cyclosporin A on I(kappa)B(alpha) Degradation and IKK Pathway in Bronchial Epithelial Cells, Monocytes, Lymphocytes and Alveolar Macrophages.
10.4046/trd.2003.54.4.449
- Author:
Ho Il YOON
1
;
Chang Hoon LEE
;
Hee Seok LEE
;
Choon Taek LEE
;
Young Whan KIM
;
Sung Koo HAN
;
Young Soo SHIM
;
Chul Gyu YOO
Author Information
1. Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Korea. cgyoo@snu.ac.kr
- Publication Type:In Vitro ; Original Article
- Keywords:
cyclosporin;
FK506;
NF-kappaB;
I(kappa)B(alpha)
- MeSH:
Antigen-Antibody Complex;
Blotting, Western;
Cyclosporine*;
Epithelial Cells*;
Immunosuppressive Agents;
Lymphocytes*;
Macrophages, Alveolar*;
Monocytes*;
NF-kappa B;
Phosphotransferases;
Tacrolimus*;
Tumor Necrosis Factor-alpha
- From:Tuberculosis and Respiratory Diseases
2003;54(4):449-458
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND: Cyclosporin A(CsA) and tacrolimus(FK506) have been widely used as immunosuppressants. The effects of CsA, or FK506, on the IkappaB/NF-kappaB pathway have been shown to vary according to the cell type. However, their effects on the IkappaB/NF-kappaB pathway have not been reported in bronchial epithelial cells. In this study, the effects of CsA and FK506 on the IkappaB/NF-kappaB pathway in bronchial epithelial cells, monocytes, lymphocytes and alveolar macrophages were evaluated. The relationship between their effects on the IkappaB/NF-kappaB pathway and IkappaB 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-alpha, LPS or IL-1beta. The I(kappa)B(alpha) expressions were assayed by Western blot analyses. The IKK activity was evaluated by an in vitro immune complex kinase assay, using GST-I(kappa)B(alpha) as the substrate. RESULTS: Neither CsA nor FK506 affected the level of I(kappa)B(alpha) expression in any of the cell types used in this study. CsA pre-treatment inhibited the TNFalpha-induced I(kappa)B(alpha) degradation in bronchial epithelial cells. In contrast, the TNFalpha-induced I(kappa)B(alpha) degradation was not affected by FK506 pre-treatment. However, FK506 suppressed the cytokine-induced I(kappa)B(alpha) degradation in the pulmonary alveolar macrophages, peripheral blood monocytes and lymphocytes. The inhibitory effect of CsA, or FK506, on I(kappa)B(alpha) degradation was not related to IKK. CONCLUSIONS: CsA and FK506 suppressed the I(kappa)B(alpha) degradation in bronchial epithelial cells, mono. cytes, lymphocytes and alveolar macrophages, so this may not be mediated through IKK.
