Inflammation, caveolae and CD38-mediated calcium regulation in human airway smooth muscle

Venkatachalem Sathish, Michael A. Thompson, Sutapa Sinha, Gary C. Sieck, Y. S. Prakash, Christina M. Pabelick

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

The pro-inflammatory cytokine tumor necrosis factor-alpha (TNFα) increases expression of CD38 (a membrane-associated bifunctional enzyme regulating cyclic ADP ribose), and enhances agonist-induced intracellular Ca2+ ([Ca2+]i) responses in human airway smooth muscle (ASM). We previously demonstrated that caveolae and their constituent protein caveolin-1 are important for ASM [Ca2+]i regulation, which is further enhanced by TNFα. Whether caveolae and CD38 are functionally linked in mediating TNFα effects is unknown. In this regard, whether the related cavin proteins (cavin-1 and -3) that maintain structure and function of caveolae play a role is also not known. In the present study, we hypothesized that TNFα effects on CD38 expression and function in human ASM involve caveolae. Caveolar fractions from isolated human ASM cells expressed CD38 and its expression was upregulated by exposure to 20ng/ml TNFα (48h). ASM cells expressed cavin-1 and cavin-3, which were also upregulated by TNFα. Knockdown of caveolin-1, cavin-1 or cavin-3 (using siRNA) all significantly reduced CD38 expression and ADP-ribosyl cyclase activity in the presence or absence of TNFα. Furthermore, caveolin-1, cavin-1 and cavin-3 siRNAs reduced [Ca2+]i responses to histamine under control conditions, and blunted the enhanced [Ca2+]i responses in TNFα-exposed cells. These data demonstrate that CD38 is expressed within caveolae and its function is linked to the caveolar regulatory proteins caveolin-1, cavin-1 and -3. The link between caveolae and CD38 is further enhanced during airway inflammation demonstrating the important role of caveolae in regulation of [Ca2+]i and contractility in the airway.

Original languageEnglish (US)
Pages (from-to)346-351
Number of pages6
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1843
Issue number2
DOIs
StatePublished - Feb 2014

Keywords

  • ADP ribosyl cyclase
  • Asthma
  • Cavin
  • Lung
  • Plasma membrane

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Inflammation, caveolae and CD38-mediated calcium regulation in human airway smooth muscle'. Together they form a unique fingerprint.

Cite this