Caveolin-1 in cytokine-induced enhancement of intracellular Ca 2+ in human airway smooth muscle

Venkatachalem Sathish, Amard J. Abcejo, Sarah Kay Vanoosten, Michael A. Thompson, Y.s. Prakash, Christina M Pabelick

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Diseases such as asthma are characterized by airway hyperresponsiveness. Enhanced airway smooth muscle (ASM) intracellular Ca 2+ ([Ca 2+] i) response to agonist stimulation leading to increased airway constriction has been suggested to contribute to airway hyperresponsiveness. Caveolae are flask-shaped plasma membrane invaginations that express the scaffolding protein caveolin and contain multiple proteins important in [Ca 2+] i signaling (e.g., agonist receptors, ion channels). We recently demonstrated that caveolae and caveolin-1 are important in [Ca 2+] i regulation in human ASM. Proinflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin (IL)-13 modulate [Ca 2+] i in ASM. We hypothesized that cytokine upregulation of caveolar signaling in ASM contributes to enhanced agonist-induced [Ca 2+] i in inflammation. Enzymatically dissociated human ASM cells were exposed to medium (control), 20 ng/ml TNF-α, or 50 ng/ml IL-13 for 24 h. Caveolae-enriched membrane fractions displayed substantial increase in caveolin-1 and -2 expressions by TNF-α and IL-13. Transfection with caveolin-1-mRed DNA substantially accelerated and increased plasma membrane caveolin-1 expression by TNF-α and to a lesser extent by IL-13. Caveolin-1 enhancement was inhibited by nuclear factor-κB and mitogen-activated protein kinase inhibitors. In fura 2-loaded ASM cells, [Ca 2+] i responses to 1μ M ACh, 10 μM histamine, or 10 nM bradykinin were all exaggerated by TNF-α as well as IL-13 exposure. However, disruption of caveolae using caveolin- 1 suppression via small-interfering RNA resulted in significant blunting of agonist-induced [Ca 2+] i responses of vehicle and TNF-α- exposed cells. These functional data were correlated to the presence of TNFR 1 receptor (but not the IL-4/IL-13 receptor) within caveolae. Overall, these results indicate that caveolin-1 plays an important role in airway inflammation by modulating the effect of specific cytokines on [Ca 2+] i.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume301
Issue number4
DOIs
StatePublished - Oct 2011

Fingerprint

Caveolin 1
Caveolae
Smooth Muscle
Interleukin-13
Cytokines
Tumor Necrosis Factor-alpha
Smooth Muscle Myocytes
Caveolin 2
Interleukin-13 Receptors
Cell Membrane
Interleukin-4 Receptors
Caveolins
Inflammation
Interleukin-1 Receptors
Fura-2
Bradykinin
Protein Kinase Inhibitors
Mitogen-Activated Protein Kinases
Ion Channels
Constriction

Keywords

  • Asthma
  • Caveolae
  • Cytokine
  • Inflammation
  • Lipid raft
  • Lung
  • Mitogenactivated protein kinase
  • Nuclear factor-κB
  • Small-interfering ribonucleic acid

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology
  • Physiology

Cite this

Caveolin-1 in cytokine-induced enhancement of intracellular Ca 2+ in human airway smooth muscle. / Sathish, Venkatachalem; Abcejo, Amard J.; Vanoosten, Sarah Kay; Thompson, Michael A.; Prakash, Y.s.; Pabelick, Christina M.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 301, No. 4, 10.2011.

Research output: Contribution to journalArticle

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