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

Bit Na Kang, K. G. Tirumurugaan, Deepak A. Deshpande, Yassine Amrani, Reynold A. Panettieri, Timothy F. Walseth, Mathur S. Kannan

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

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-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.

Original languageEnglish (US)
Pages (from-to)E170-E179
JournalFASEB Journal
Volume20
Issue number7
DOIs
StatePublished - May 2006

Keywords

  • Airway
  • Cytokines
  • Glucocorticoid
  • Smooth muscle
  • Transcription factors

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