Regulation of CD38 expression in human airway smooth muscle cells: Role of class I phosphatidylinositol 3 kinases

Joseph A. Jude, Krishnaswamy G. Tirumurugaan, Bit Na Kang, Reynold A. Panettieri, Timothy F. Walseth, Mathur S. Kannan

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

The ADP-ribosyl cyclase activity of CD38 generates cyclic ADP-ribose, a Ca2+-mobilizing agent. In human airway smooth muscle (HASM) cells, TNF-α mediates CD38 expression through mitogen-activated protein kinases and NF-κB and AP-1. The phosphatidylinositol-3 kinase/Akt (PI3K/Akt) pathway is involved in TNF-α signaling and contributes to airway hyperresponsiveness and airway remodeling. We hypothesized that PI3Ks mediate CD38 expression and are involved in the differential induction of CD38 by TNF-α in asthmatic HASM cells. HASM cells were treated with pan-PI3K inhibitors (LY294002 or wortmannin) or class I-selective (GDC0941) or isoform-selective PI3K inhibitors (p110α-PIK-75 and p110β-TGX- 221)with orwithout TNF-α. HASM cells were transfected with a catalytically active form of PI3K or phosphatase and tensin homolog (PTEN) or nontargeting or p110 isoform-targeting siRNAs before TNF-β exposure. CD38 expression and activation of Akt,NF-κB, and AP-1 were determined. LY294002 and wortmannin inhibited TNFα- induced Akt activation, whereas only LY294002 inhibited CD38 expression. P110 expression caused Akt activation and basal and TNF-β-induced CD38 expression, whereas PTEN expression attenuated Akt activation and CD38 expression. Expression levels of p110 isoforms α, β, and δ were comparable in nonasthmatic and asthmatic HASM cells. Silencing of p110α or -δ, but not p110β, resulted in comparable attenuation of TNF-α-induced CD38 expression in asthmatic and nonasthmatic cells. NF-κB and AP-1 activation were unaltered by the PI3K inhibitors. In HASM cells, regulation of CD38 expression occurs by specific class I PI3K isoforms, independent of NF-κB or AP-1 activation, and PI3K signaling may not be involved in the differential elevation of CD38 in asthmatic HASM cells.

Original languageEnglish (US)
Pages (from-to)427-435
Number of pages9
JournalAmerican journal of respiratory cell and molecular biology
Volume47
Issue number4
DOIs
StatePublished - Oct 2012

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

Keywords

  • Airway
  • CD38
  • PI3 kinase
  • PI3 kinase isoforms
  • Smooth muscle

Fingerprint Dive into the research topics of 'Regulation of CD38 expression in human airway smooth muscle cells: Role of class I phosphatidylinositol 3 kinases'. Together they form a unique fingerprint.

Cite this