Transcriptional regulation of CD38 expression by tumor necrosis factor- in human airway smooth muscle cells: role of NF-B and sensitivity to glucocorticoids

Authors:
Kang BN, Tirumurugaan KG, Deshpande DA, Amrani Y, Panettieri RA, Walseth TF, Kannan MS
In:
Source: FASEB J
Publication Date: (2006)
Issue: 20(7): 1000-2
Research Area:
Cancer Research/Cell Biology
Cells used in publication:
SMC, airway (HASM), human
Species: human
Tissue Origin: lung
Platform:
Nucleofector® I/II/2b
Abstract
The transmembrane glycoprotein CD38 catalyzes the synthesis( )of the calcium mobilizing molecule cyclic ADP-ribose from NAD.( )In human airway smooth muscle (HASM) cells, the expression and( )function of CD38 are augmented by the inflammatory cytokine( )tumor necrosis factor-alpha (TNF-), leading to increased intracellular( )calcium response to agonists. A glucocorticoid response element( )in the CD38 gene has been computationally described, providing( )evidence for transcriptional regulation of its expression. In( )the present study, we investigated the effects of dexamethasone,( )a glucocorticoid, on CD38 expression and ADP-ribosyl cyclase( )activity in HASM cells stimulated with TNF-. In HASM cells,( )TNF- augmented CD38 expression and ADP-ribosyl cyclase activity,( )which were attenuated by dexamethasone. TNF- increased NF-B( )expression and its activation, and dexamethasone partially reversed( )these effects. TNF- increased the expression of IB, and dexamethasone( )increased it further. An inhibitor of NF-B activation or transfection( )of cells with IB mutants decreased TNF--induced CD38 expression.( )The results indicate that TNF--induced CD38 expression involves( )NF-B expression and its activation and dexamethasone inhibits( )CD38 expression through NF-B-dependent and -independent mechanisms.--( )Kang, B.-N., Tirumurugaan, K. G., Deshpande, D. A., Amrani,( )Y., Panettieri, R. A., Walseth, T. F., Kannan, M. S. Transcriptional( )regulation of CD38 expression by tumor necrosis factor- in human( )airway smooth muscle cells: role of NF-B and sensitivity to( )glucocorticoids.( ).