Tuberc Respir Dis.  2003 Apr;54(4):449-458.

Effect of FK506 and Cyclosporin A on I(kappa)B(alpha) Degradation and IKK Pathway in Bronchial Epithelial Cells, Monocytes, Lymphocytes and Alveolar Macrophages

• Yoon HI
• Lee CH
• Lee HS
• Lee CT
• Kim YW
• Han SK
• Shim YS
• Yoo CG

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.

Keyword

cyclosporin; FK506; NF-kappaB; I(kappa)B(alpha)

MeSH Terms

Antigen-Antibody Complex
Blotting, Western
Cyclosporine*
Epithelial Cells*
Immunosuppressive Agents
Lymphocytes*
Macrophages, Alveolar*
Monocytes*
NF-kappa B
Phosphotransferases
Tacrolimus*
Tumor Necrosis Factor-alpha
Antigen-Antibody Complex
Cyclosporine
Immunosuppressive Agents
NF-kappa B
Phosphotransferases
Tacrolimus
Tumor Necrosis Factor-alpha