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

American Journal of Respiratory Cell and Molecular Biology
J A JudeMathur S Kannan

Abstract

The ADP-ribosyl cyclase activity of CD38 generates cyclic ADP-ribose, a Ca(2+)-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 or without 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-α exposure. CD38 expression and activation of Akt, NF-κB, and AP-1 were determined. LY294002 and wortmannin inhibited TNF-α-induced Akt activation, whereas only LY294002 inhibited CD38 expression. P110 expression caused Akt activation and basal and TNF-α-induced CD38 expression, whereas PTEN expression attenuated Akt activation and CD38 expressio...Continue Reading

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Citations

Dec 6, 2012·Journal of Allergy·Joseph A JudeMathur S Kannan
Jan 17, 2015·Canadian Journal of Physiology and Pharmacology·Alonso G P GuedesMathur S Kannan
May 6, 2016·American Journal of Respiratory Cell and Molecular Biology·Joseph JudeReynold Panettieri
Dec 16, 2016·American Journal of Respiratory Cell and Molecular Biology·Edwin J YooReynold A Panettieri
Jun 29, 2016·British Journal of Pharmacology·Cynthia J Koziol-WhiteReynold A Panettieri
Apr 5, 2019·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Yuki NishimotoYasuo Kizawa
Jun 16, 2015·PloS One·Mark E WylamY S Prakash
Jan 7, 2020·Current Topics in Medicinal Chemistry·Rammohan R Y Bheemanaboina
Mar 27, 2018·Mediators of Inflammation·Deepak A DeshpandeMathur S Kannan
Oct 31, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Richard GraeffMathur Kannan
Jun 2, 2020·Current Opinion in Pharmacology·Alonso Gp GuedesMathur S Kannan

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