Transient receptor potential vanilloid 1 activation induces inflammatory cytokine release in corneal epithelium through MAPK signaling

Fan Zhang, Hua Yang, Zheng Wang, Stefan Mergler, Hongshan Liu, Tetsuya Kawakita, Souvenir D. Tachado, Zan Pan, José E. Capó-Aponte, Uwe Pleyer, Henry Koziel, Winston W.Y. Kao, Peter S. Reinach

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88 Citations (Scopus)

Abstract

In certain epithelial tissues, activation of transient receptor potential (TRP) vanilloid subtype 1 (TRPV1) by noxious stimuli induces proinflammatory cytokine release, which helps to mitigate the challenge. While the corneal epithelium elicits such responses to a variety of challenges, it remains unknown whether TRPV1 mediates pro-inflammatory cytokine secretion. Accordingly, we probed for TRPV1 expression and function in human (HCEC) and rabbit corneal epithelial cell (RCEC) lines, in their primary counterparts, and in human and mouse corneal epithelium in situ. Cell membrane and perinuclear TRPV1 expression was detected in all preparations and its identity verified by Western blot analysis. Capsaicin (CAP) (1-10 μM) increased nonselective cation channel whole cell currents (2.5-fold ± 0.5-fold between -60 and 130 mV), resulting in calcium transients that were fully blocked by the TRPV1 antagonists capsazepine (CPZ) and ruthenium red, or removal of extracellular calcium. Another signaling event involved transient activation of global mitogen-activated protein kinase (MAPK) superfamily, which was followed by up to 3.3- and 9-fold increases in interleukins (IL)-6 and -8 release, respectively. Such increases in inflammatory mediators' release were suppressed by exposure to CPZ or MAPK inhibitors, or removal of Ca2+. Taken together, TRPV1 receptors may play a role in mediating corneal epithelial inflammatory mediator secretion and subsequent hyperalgesia.

Original languageEnglish
Pages (from-to)730-739
Number of pages10
JournalJournal of Cellular Physiology
Volume213
Issue number3
DOIs
Publication statusPublished - 2007 Dec

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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    Zhang, F., Yang, H., Wang, Z., Mergler, S., Liu, H., Kawakita, T., Tachado, S. D., Pan, Z., Capó-Aponte, J. E., Pleyer, U., Koziel, H., Kao, W. W. Y., & Reinach, P. S. (2007). Transient receptor potential vanilloid 1 activation induces inflammatory cytokine release in corneal epithelium through MAPK signaling. Journal of Cellular Physiology, 213(3), 730-739. https://doi.org/10.1002/jcp.21141