Tumor necrosis factor α induces α1B-adrenergic receptor expression in keratinocytes

Cytokine. 2020 Jan:125:154851. doi: 10.1016/j.cyto.2019.154851. Epub 2019 Sep 11.

Abstract

Keratinocytes produce cytokines and nerve growth factor (NGF) as part of a repair response to injury, disease or stress, and express alpha1-adrenoceptors (α1-AR). The expression of these receptors is elevated in some inflammatory diseases and chronic pain conditions. In this study, we investigated whether inflammatory signalling affects α1-AR expression in keratinocytes in vitro. Tumor necrosis factor α (TNFα) was administered to human keratinocytes, after which the levels of other key pro-inflammatory cytokines and NGF were measured. The production of these cytokines and NGF increased in cells treated with TNFα compared to untreated cells. Furthermore, exposure to TNFα increased gene expression of the α1-AR subtype B in keratinocytes. Our results suggest that inflammatory cytokines released during injury stimulate α1-AR expression in keratinocytes. The up-regulation of α1-AR may amplify the adrenergic sensitivity of these cells to catecholamines released during sympathetic nervous system activation after injury which, in turn, could heighten the inflammatory response.

Keywords: Alpha(1)-adrenergic receptor; In vitro; Inflammatory cytokines; Keratinocytes; Tumor necrosis factor α.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cell Line
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / genetics
  • Humans
  • Inflammation / metabolism
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism
  • Keratinocytes / drug effects*
  • Keratinocytes / metabolism*
  • Middle Aged
  • Nerve Growth Factor / genetics
  • Nerve Growth Factor / metabolism
  • Nerve Growth Factors / metabolism*
  • Receptors, Adrenergic, alpha-1 / genetics
  • Receptors, Adrenergic, alpha-1 / metabolism*
  • Tumor Necrosis Factor-alpha / pharmacology*

Substances

  • CXCL8 protein, human
  • Cytokines
  • IL6 protein, human
  • Interleukin-1beta
  • Interleukin-6
  • Interleukin-8
  • NGF protein, human
  • Nerve Growth Factors
  • Receptors, Adrenergic, alpha-1
  • Tumor Necrosis Factor-alpha
  • Nerve Growth Factor