A new role of the oxytocin system in human skin stress responses and implications for atopic dermatitis

Abstract

The neuropeptide hormone oxytocin (OXT) mediates a wide spectrum of tissue-specific actions, ranging from cell growth, cell differentiation, sodium excretion to stress responses, reproduction and complex social behaviors. OXT is known to modulate neuroendocrine stress responses, inflammatory processes and to counteract the hypothalamus–pituitary–adrenal axis. Recently, OXT expression has been detected in keratinocytes, but its function is still unexplored in human skin.Here, we show that both, OXT and its receptor, are expressed in primary human skin cells. OXT induces dose-dependent calcium-fluxes in dermal fibroblasts and keratinocytes, indicating that the OXT receptor (OXTR) is functionally expressed in both cell types. In order to investigate potential OXT-mediated functions in skin stress responses, we performed OXTR-knockdown experiments. OXTR-knockdown in dermal fibroblasts and keratinocytes lead to elevated levels of reactive oxygen species and reduced levels of glutathione. In keratinocytes, an increased release of proinflammatory cytokines, such as IL-6, RANTES, and CXCL10 was observed.In conclusion, atopic dermatitis, a multifactorial inflammatory skin disease, is characterized, among others, by an increased susceptibility to oxidative stress. We detected a reduced expression of the OXT system in lesional and peri-lesional atopic skin suggesting a clinical relevance in skin homeostasis.