TRPV3 Channel in Keratinocytes in Scars with Post-Burn Pruritus

Int J Mol Sci. 2017 Nov 15;18(11):2425. doi: 10.3390/ijms18112425.

Abstract

Post-burn pruritus is a common and distressing sequela of burn scars. Empirical antipruritic treatments usually fail to have a satisfactory outcome because of their limited selectivity and possible side effects. Therefore, novel drug targets need to be identified. Here, we aimed to investigate the possible role of protease-activated receptor 2 (PAR2) and transient receptor potential vanniloid 3 (TRPV3), along with the relation of TRPV3 to thymic stromal lymphopoietin (TSLP). Specimens from normal (unscarred) or burn-scarred (with or without pruritus) tissue were obtained from burn patients for this study. In each sample, the keratinocytes were isolated and cultured, and the intracellular Ca2+ level at the time of stimulation of each factor was quantified and the interaction was screened. PAR2 function was reduced by antagonism of TRPV3. Inhibiting protein kinase A (PKA) and protein kinase C (PKC) reduced TRPV3 function. TSLP mRNA and protein, and TSLPR protein expressions, increased in scars with post-burn pruritus, compared to scars without it or to normal tissues. In addition, TRPV1 or TRPV3 activation induced increased TSLP expression. Conclusively, TRPV3 may contribute to pruritus in burn scars through TSLP, and can be considered a potential therapeutic target for post-burn pruritus.

Keywords: post-burn pruritus; protease-activated receptor 2; thymic stromal lymphopoietin; transient receptor potential vanniloid 3.

MeSH terms

  • Adolescent
  • Adult
  • Burns / complications*
  • Burns / metabolism*
  • Burns / pathology
  • Calcium / metabolism
  • Cells, Cultured
  • Child
  • Cicatrix / etiology*
  • Cicatrix / metabolism*
  • Cicatrix / pathology
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Cytokines / metabolism
  • Epidermis / pathology
  • Female
  • Humans
  • Ion Channel Gating
  • Keratinocytes / metabolism*
  • Keratinocytes / pathology
  • Male
  • Middle Aged
  • Phospholipase C beta / metabolism
  • Protein Kinase C / metabolism
  • Pruritus / etiology*
  • Pruritus / metabolism*
  • Pruritus / pathology
  • Receptor, PAR-2
  • Receptors, Cytokine / metabolism
  • TRPV Cation Channels / metabolism*
  • Young Adult

Substances

  • Cytokines
  • Receptor, PAR-2
  • Receptors, Cytokine
  • TRPV Cation Channels
  • TRPV1 protein, human
  • TRPV3 protein, human
  • Cyclic AMP-Dependent Protein Kinases
  • Protein Kinase C
  • Phospholipase C beta
  • thymic stromal lymphopoietin
  • Calcium