Activation of epidermal vanilloid receptor-1 induces release of proinflammatory mediators in human keratinocytes

Michael D. Southall, Tao Li, Lera S. Gharibova, Yong Pei, Grant D. Nicol, Jeffrey B. Travers

Research output: Contribution to journalArticle

238 Scopus citations

Abstract

During dermal injury and the associated trauma a number of compounds are released that can mediate the inflammatory response. Determining the cellular mechanisms that initiate the inflammatory responses to acute keratinocyte damage is important for understanding the regulation of epidermal inflammation. The recently cloned vanilloid receptor-1 (VR1) is a polymodal receptor, responding to thermal, pH, or vanilloids such as capsaicin stimulation. Although VR1 has been localized only on sensory neurons and within the central nervous system, recent evidence suggests a functional VR1 is expressed in human skin and epidermal cells. Using reverse transcription-polymerase chain reaction and immunoblotting we report that human keratinocytes and the human keratinocyte cell line Ha-CaT express VR1. Consistent with neuronal VR1, activation of epidermal VR1 by capsaicin induced a calcium influx. Treating HaCaT cells with capsaicin resulted in a dose-dependent expression of cyclooxygenase-2 (COX-2), whereas pretreatment with the VR1 receptor antagonist capsazepine abolished the capsaicin-stimulated increase in COX-2 expression. Furthermore, the capsaicin-induced expression of COX-2 was dependent on extracellular calcium. Activation of the epidermal VR1 by capsaicin also resulted in an increased release of interleukin-8 and prostaglandin E2, and the stimulated release was attenuated by capsazepine. The finding that VR1 is expressed by keratinocytes is of great importance because it expands the putative role of VR1 beyond that of pain perception. Our results suggest that VR1 expression in keratinocytes may have a role in the inflammation that occurs secondary to epidermal damage or insult, and thus may function as a sensor for noxious cutaneous stimulation.

Original languageEnglish (US)
Pages (from-to)217-222
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume304
Issue number1
DOIs
StatePublished - Jan 1 2003

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ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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