TY - JOUR
T1 - Transcriptional regulation of CD38 expression by tumor necrosis factor-α in human airway smooth muscle cells
T2 - Role of NF-κB and sensitivity to glucocorticoids
AU - Kang, Bit Na
AU - Tirumurugaan, K. G.
AU - Deshpande, Deepak A.
AU - Amrani, Yassine
AU - Panettieri, Reynold A.
AU - Walseth, Timothy F.
AU - Kannan, Mathur S.
PY - 2006/5
Y1 - 2006/5
N2 - 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-α), 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-α. In HASM cells, TNF-α augmented CD38 expression and ADP-ribosyl cyclase activity, which were attenuated by dexamethasone. TNF-α increased NF-κB expression and its activation, and dexamethasone partially reversed these effects. TNF-α increased the expression of IκBα, and dexamethasone increased it further. An inhibitor of NF-κB activation or transfection of cells with IκB mutants decreased TNF-α-induced CD38 expression. The results indicate that TNF-α-induced CD38 expression involves NF-κB expression and its activation and dexamethasone inhibits CD38 expression through NF-κB-dependent and -independent mechanisms.
AB - 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-α), 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-α. In HASM cells, TNF-α augmented CD38 expression and ADP-ribosyl cyclase activity, which were attenuated by dexamethasone. TNF-α increased NF-κB expression and its activation, and dexamethasone partially reversed these effects. TNF-α increased the expression of IκBα, and dexamethasone increased it further. An inhibitor of NF-κB activation or transfection of cells with IκB mutants decreased TNF-α-induced CD38 expression. The results indicate that TNF-α-induced CD38 expression involves NF-κB expression and its activation and dexamethasone inhibits CD38 expression through NF-κB-dependent and -independent mechanisms.
KW - Airway
KW - Cytokines
KW - Glucocorticoid
KW - Smooth muscle
KW - Transcription factors
UR - http://www.scopus.com/inward/record.url?scp=33845632790&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33845632790&partnerID=8YFLogxK
U2 - 10.1096/fj.05-4585fje
DO - 10.1096/fj.05-4585fje
M3 - Article
C2 - 16571778
AN - SCOPUS:33845632790
SN - 0892-6638
VL - 20
SP - E170-E179
JO - FASEB Journal
JF - FASEB Journal
IS - 7
ER -