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TRPV4-mediated calcium influx and ciliary activity in human native airway epithelial cells.

Alenmyr, Lisa LU ; Uller, Lena LU ; Greiff, Lennart LU ; Högestätt, Edward LU and Zygmunt, Peter LU (2014) In Basic & Clinical Pharmacology & Toxicology 114(2). p.210-216
Abstract
The transient receptor potential, vanilloid 4 (TRPV4), is a calcium permeable ion channel expressed in airway epithelial cells. Based on studies of cell lines and animals, TRPV4 has been suggested to play a role in the regulation of ciliary beat frequency (CBF). Whether the same is true for human ciliated epithelial cells is not known. Therefore, the aim was to examine the expression and function of TRPV4 in human native nasal epithelial cells. Expression of TRPV4 mRNA in nasal epithelial cells and in the cell lines BEAS2B and 16HBE was confirmed by quantitative real-time PCR. A marked apical TRPV4 immunoreactivity was observed in nasal epithelial cells using immunocytochemistry. Responses to pharmacological modulation of TRPV4 were... (More)
The transient receptor potential, vanilloid 4 (TRPV4), is a calcium permeable ion channel expressed in airway epithelial cells. Based on studies of cell lines and animals, TRPV4 has been suggested to play a role in the regulation of ciliary beat frequency (CBF). Whether the same is true for human ciliated epithelial cells is not known. Therefore, the aim was to examine the expression and function of TRPV4 in human native nasal epithelial cells. Expression of TRPV4 mRNA in nasal epithelial cells and in the cell lines BEAS2B and 16HBE was confirmed by quantitative real-time PCR. A marked apical TRPV4 immunoreactivity was observed in nasal epithelial cells using immunocytochemistry. Responses to pharmacological modulation of TRPV4 were assessed with calcium imaging and CBF measurements. The TRPV4 agonist GSK1016790A produced concentration-dependent calcium responses in TRPV4-expressing HEK293, BEAS2B and 16HBE cells, and the TRPV4 antagonist HC067047 caused a rightward shift of the GSK1016790A concentration-response curves. Nasal epithelial cells responded to the TRPV4 agonist GSK1016790A with increased intracellular calcium signals and increased CBF, followed by cessation of ciliary beating and cell death. These effects were prevented or inhibited by the TRPV4 antagonist HC067047, the TRP channel blocker ruthenium red or removal of extracellular calcium. We conclude that TRPV4 is expressed in human primary nasal epithelial cells and modulates epithelial calcium levels and CBF. Thus, TRPV4 may participate in mucociliary clearance and airway protection. However, exaggerated activation of TRPV4 may result in epithelial cell death. This article is protected by copyright. All rights reserved. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
Basic & Clinical Pharmacology & Toxicology
volume
114
issue
2
pages
210 - 216
publisher
Wiley-Blackwell
external identifiers
  • wos:000329319000009
  • pmid:24034343
  • scopus:84891659190
ISSN
1742-7843
DOI
10.1111/bcpt.12135
language
English
LU publication?
yes
id
83f240cc-b504-4c07-a853-177b28e57e57 (old id 4065888)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24034343?dopt=Abstract
date added to LUP
2013-10-02 15:16:46
date last changed
2017-11-12 03:16:33
@article{83f240cc-b504-4c07-a853-177b28e57e57,
  abstract     = {The transient receptor potential, vanilloid 4 (TRPV4), is a calcium permeable ion channel expressed in airway epithelial cells. Based on studies of cell lines and animals, TRPV4 has been suggested to play a role in the regulation of ciliary beat frequency (CBF). Whether the same is true for human ciliated epithelial cells is not known. Therefore, the aim was to examine the expression and function of TRPV4 in human native nasal epithelial cells. Expression of TRPV4 mRNA in nasal epithelial cells and in the cell lines BEAS2B and 16HBE was confirmed by quantitative real-time PCR. A marked apical TRPV4 immunoreactivity was observed in nasal epithelial cells using immunocytochemistry. Responses to pharmacological modulation of TRPV4 were assessed with calcium imaging and CBF measurements. The TRPV4 agonist GSK1016790A produced concentration-dependent calcium responses in TRPV4-expressing HEK293, BEAS2B and 16HBE cells, and the TRPV4 antagonist HC067047 caused a rightward shift of the GSK1016790A concentration-response curves. Nasal epithelial cells responded to the TRPV4 agonist GSK1016790A with increased intracellular calcium signals and increased CBF, followed by cessation of ciliary beating and cell death. These effects were prevented or inhibited by the TRPV4 antagonist HC067047, the TRP channel blocker ruthenium red or removal of extracellular calcium. We conclude that TRPV4 is expressed in human primary nasal epithelial cells and modulates epithelial calcium levels and CBF. Thus, TRPV4 may participate in mucociliary clearance and airway protection. However, exaggerated activation of TRPV4 may result in epithelial cell death. This article is protected by copyright. All rights reserved.},
  author       = {Alenmyr, Lisa and Uller, Lena and Greiff, Lennart and Högestätt, Edward and Zygmunt, Peter},
  issn         = {1742-7843},
  language     = {eng},
  number       = {2},
  pages        = {210--216},
  publisher    = {Wiley-Blackwell},
  series       = {Basic & Clinical Pharmacology & Toxicology},
  title        = {TRPV4-mediated calcium influx and ciliary activity in human native airway epithelial cells.},
  url          = {http://dx.doi.org/10.1111/bcpt.12135},
  volume       = {114},
  year         = {2014},
}