Ghrelin protects against contact dermatitis and psoriasiform skin inflammation by antagonizing TNF-\u03b1/NF-\u03baB signaling pathways

Ruize Qu,Long Liu,Linlin Guo,Jianying Chen,Krasimir Vasilev,Yufeng Fu,Jiankang Cao,Jiangfan Peng,Wenhan Wang,Yunpeng Zhao,Yuhua Li,Xiaomin Chen,Cheng Qiu,Jingxi Chen,Peng Li,Weiwei Li,Gengyin Zhou,Jing Hu

doi:10.1038/s41598-018-38174-2

Abstract

Contact dermatitis and psoriasis are skin disorders caused by immune dysregulation, yet much remains unknown about their underlying mechanisms. Ghrelin, a recently discovered novel peptide and potential endogenous anti-inflammatory factor expressed in the epidermis, is involved in skin repair and disease. In this study, we investigated the expression pattern and therapeutic effect of ghrelin in both contact dermatitis and psoriasis mouse models induced by oxazolone (OXA) and imiquimod (IMQ), respectively, and in TNF-α-stimulated RAW264.7 macrophages, NHEKs and skin fibroblasts. Ghrelin expression was reduced in both the OXA-induced contact dermatitis and IMQ-induced psoriasis mouse models. Furthermore, treatment with ghrelin attenuated skin inflammation in both the contact dermatitis and psoriasis mouse models. Mice administered PBS after OXA- or IMQ-induced model generation exhibited typical skin inflammation, whereas ghrelin treatment in these mouse models substantially decreased the dermatitis phenotype. In addition, exogenous ghrelin attenuated the inflammatory reaction induced by TNF-α in RAW264.7 cells. Moreover, ghrelin administration limited activation of NF-κB signaling. In summary, ghrelin may represent a potential molecular target for the prevention and treatment of inflammatory skin diseases, including contact dermatitis and psoriasis.

Highlights

Dermatitis, including contact dermatitis and psoriasis, is a common inflammatory skin disorder affecting millions of people worldwide[1,2]
Given the critical role of TNF-α in the initiation and progression of inflammation and the positive role reported for ghrelin in some inflammatory diseases, in this study, we aimed to examine whether ghrelin affects contact dermatitis and psoriasis by limiting TNF-α and to explore its molecular mechanisms, which may highlight a new direction of study for the treatment of both contact dermatitis and psoriasis
These results indicate that ghrelin is found in skin cells such as epidermal cells and macrophages, while inflammatory cytokines like TNF-α lead to loss of ghrelin expression in the skin

Summary

Introduction

Dermatitis, including contact dermatitis and psoriasis, is a common inflammatory skin disorder affecting millions of people worldwide[1,2]. TNF-α is a well-known inflammatory factor involved in a variety of inflammatory diseases[11,12,13] It is primarily produced by macrophages during inflammation and exerts negative effects[14,15,16]. TNF-α has been reported to be part of the inflammatory process of skin inflammatory diseases, and inhibition of TNF-α yields positive effects on the treatment of dermatitis[20,21,22,23]. Given the critical role of TNF-α in the initiation and progression of inflammation and the positive role reported for ghrelin in some inflammatory diseases, in this study, we aimed to examine whether ghrelin affects contact dermatitis and psoriasis by limiting TNF-α and to explore its molecular mechanisms, which may highlight a new direction of study for the treatment of both contact dermatitis and psoriasis

Objectives

Methods

Results

Conclusion