CD38 in the pathogenesis of allergic airway disease: Potential therapeutic targets

Deepak A. Deshpande, Alonso G P Guedes, Frances E. Lund, Subbaya Subramanian, Timothy F. Walseth, Mathur S. Kannan

Research output: Contribution to journalReview article

14 Scopus citations

Abstract

CD38 is an ectoenzyme that catalyzes the conversion of β-nicotinamide adenine dinucleotide (β-NAD) to cyclic adenosine diphosphoribose (cADPR) and adenosine diphosphoribose (ADPR) and NADP to nicotinic acid adenine dinucleotide phosphate (NAADP) and adenosine diphosphoribose-2′-phosphate (ADPR-P). The metabolites of NAD and NADP have roles in calcium signaling in different cell types including airway smooth muscle (ASM) cells. In ASM cells, inflammatory cytokines augment CD38 expression and to a greater magnitude in cells from asthmatics, indicating a greater capacity for the generation of cADPR and ADPR in ASM from asthmatics. CD38 deficient mice develop attenuated airway responsiveness to inhaled methacholine following allergen sensitization and challenge compared to wild-type mice indicating its potential role in asthma. Regulation of CD38 expression in ASM cells is achieved by mitogen activated protein kinases, specific isoforms of PI3 kinases, the transcription factors NF-κB and AP-1, and post-transcriptionally by microRNAs. This review will focus on the role of CD38 in intracellular calcium regulation in ASM, contribution to airway inflammation and airway hyperresponsiveness in mouse models of allergic airway inflammation, the transcriptional and post-transcriptional mechanisms of regulation of expression, and outline approaches to inhibit its expression and activity.

Original languageEnglish (US)
Pages (from-to)116-126
Number of pages11
JournalPharmacology and Therapeutics
Volume172
DOIs
StatePublished - Apr 1 2017
Externally publishedYes

Keywords

  • Airway smooth muscle
  • Asthma
  • Calcium regulation
  • CD38
  • MicroRNAs

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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  • Cite this

    Deshpande, D. A., Guedes, A. G. P., Lund, F. E., Subramanian, S., Walseth, T. F., & Kannan, M. S. (2017). CD38 in the pathogenesis of allergic airway disease: Potential therapeutic targets. Pharmacology and Therapeutics, 172, 116-126. https://doi.org/10.1016/j.pharmthera.2016.12.002