Tumor necrosis factor α induces α_1B-adrenergic receptor expression in keratinocytes

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.