title: Oxytocin modulates proliferation and stress responses of human skin cells: 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 behaviour. Recently, OXT expression was detected in keratinocytes, but expression of its receptor and function are still unexplored in human skin. Here, we showed that both OXT and its receptor are expressed in primary human dermal fibroblasts and keratinocytes. OXT-induced dose-dependent calcium fluxes in both cell types demonstrating that the OXT receptor (OXTR) is functionally expressed. We also showed that OXT decreases proliferation of dermal fibroblasts and keratinocytes in a dose-dependent manner. In order to further investigate OXT-mediated functions in skin cells, we performed OXTR knockdown experiments. OXTR knockdown in dermal fibroblasts and keratinocytes led to elevated levels of reactive oxygen species and reduced levels of glutathione (GSH). Moreover, OXTR-depleted keratinocytes exhibited an increased release of the pro-inflammatory cytokines IL6, CCL5 and CXCL10. Our data indicate that the OXT system modulates key processes which are dysregulated in atopic dermatitis (AD) such as proliferation, inflammation and oxidative stress responses. Furthermore, we detected a downregulation of the OXT system in peri-lesional and lesional atopic skin. Taken together, these data suggest that the OXT system is a novel neuroendocrine mediator in human skin homoeostasis and clinically relevant to stressed skin conditions like AD.
authors.affiliation: Beiersdorf AG, Research Skin Care, Hamburg, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Deing
authors.forename: Dennis
authors.initials: D
authors.lastname: Roggenkamp
authors.forename: Jochen
authors.initials: J
authors.lastname: Kühnl
authors.forename: Alisa
authors.initials: A
authors.lastname: Gruschka
authors.forename: Franz
authors.initials: F
authors.lastname: Stäb
authors.forename: Horst
authors.initials: H
authors.lastname: Wenck
authors.forename: Alexander
authors.initials: A
authors.lastname: Bürkle
authors.forename: Gitta
authors.initials: G
authors.lastname: Neufang
mesh_terms: D000328:Adult; D002118:Calcium / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000378:metabolism* / Q000503:physiopathology*; D005260:Female; D005347:Fibroblasts / Q000166:cytology; D005978:Glutathione / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D015603:Keratinocytes / Q000166:cytology; D008297:Male; D008856:Microscopy, Fluorescence; D018384:Oxidative Stress; D010121:Oxytocin / Q000378:metabolism / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D018045:Receptors, Oxytocin / Q000235:genetics; D012867:Skin / Q000378:metabolism*; D014466:Ultraviolet Rays; D055815:Young Adult
chemical_list: D016207:Cytokines; D017382:Reactive Oxygen Species; D018045:Receptors, Oxytocin; D010121:Oxytocin; D005978:Glutathione; D002118:Calcium