Oxytocin modulates proliferation and stress responses of human skin cells: implications for atopic dermatitis
Verena Deing1, Dennis Roggenkamp, Jochen Kühnl
1Beiersdorf AG, Research Skin Care, Hamburg, Germany.
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.
Insights
The oxytocin (OXT) system is newly found in human skin, regulating cell growth and inflammation. Its downregulation is linked to atopic dermatitis, suggesting a role in skin homeostasis and stress.
Area of Science:
- Neuroendocrinology
- Dermatology
- Cell Biology
Background:
- Oxytocin (OXT) is a neuropeptide hormone with diverse physiological roles.
- OXT and its receptor (OXTR) expression and function in human skin remain largely uncharacterized.
- Recent findings suggest OXT expression in keratinocytes, prompting further investigation.
Purpose of the Study:
- To investigate the expression and function of the OXT system in human skin cells (fibroblasts and keratinocytes).
- To determine the role of OXT and OXTR in skin cell proliferation, oxidative stress, and inflammation.
- To explore the potential involvement of the OXT system in atopic dermatitis (AD).
Main Methods:
- Detection of OXT and OXTR expression in primary human dermal fibroblasts and keratinocytes.
- Assessment of OXT-induced calcium fluxes to confirm OXTR functionality.
- Dose-dependent proliferation assays for fibroblasts and keratinocytes.
- OXTR knockdown experiments to evaluate effects on reactive oxygen species (ROS), glutathione (GSH), and pro-inflammatory cytokines (IL6, CCL5, CXCL10).
- Analysis of OXT system expression in lesional and peri-lesional atopic skin.
Main Results:
- Both OXT and OXTR are expressed in human dermal fibroblasts and keratinocytes, with functional OXTR mediating calcium signaling.
- OXT dose-dependently inhibits proliferation of both cell types.
- OXTR knockdown increases ROS levels, decreases GSH levels, and enhances pro-inflammatory cytokine release from keratinocytes.
- The OXT system is downregulated in atopic skin, particularly in lesional areas.
Conclusions:
- The OXT system is a novel neuroendocrine regulator of human skin homeostasis.
- OXT signaling influences key cellular processes like proliferation, oxidative stress, and inflammation in the skin.
- Dysregulation of the OXT system is implicated in the pathogenesis of atopic dermatitis and other stressed skin conditions.
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