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Inhibitory Effects of a Novel Chrysin-Derivative, CPD 6, on Acute and Chronic Skin Inflammation.

ABSTRACT: The skin is an important physiological barrier against external stimuli, such as ultraviolet radiation (UV), xenobiotics, and bacteria. Dermal inflammatory reactions are associated with various skin disorders, including chemical-induced irritation and atopic dermatitis. Modulation of skin inflammatory response is a therapeutic strategy for skin diseases. Here, we synthesized chrysin-derivatives and identified the most potent derivative of Compound 6 (CPD 6). We evaluated its anti-inflammatory effects in vitro cells of macrophages and keratinocytes, and in vivo dermatitis mouse models. In murine macrophages stimulated by lipopolysaccharide (LPS), CPD 6 significantly attenuated the release of inflammatory mediators such as nitric oxide (NO) (IC₅₀ for NO inhibition: 3.613 ?M) and other cytokines. In cultured human keratinocytes, CPD 6 significantly attenuated the release of inflammatory cytokines induced by the combination of IFN-? and TNF-?, UV irradiation, or chemical irritant stimulation. CPD 6 inhibited NF?B and JAK2/STAT1 signaling pathways, and activated Nrf2/HO-1 signaling. In vivo relevancy of anti-inflammatory effects of CPD 6 was observed in acute and chronic skin inflammation models in mice. CPD 6 showed significant anti-inflammatory properties both in vitro cells and in vivo dermatitis animal models, mediated by the inhibition of the NF?B and JAK2-STAT1 pathways and activation of Nrf2/HO-1 signaling. We propose that the novel chrysin-derivative CPD 6 may be a potential therapeutic agent for skin inflammation.

SUBMITTER: Yu CH

PROVIDER: S-EPMC6600461 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Inhibitory Effects of a Novel Chrysin-Derivative, CPD 6, on Acute and Chronic Skin Inflammation.

Yu Chan-Hee CH Suh Beomseon B Shin Iljin I Kim Eun-Hye EH Kim Donghyun D Shin Young-Jun YJ Chang Sun-Young SY Baek Seung-Hoon SH Kim Hyoungsu H Bae Ok-Nam ON

International journal of molecular sciences 20190528 11

The skin is an important physiological barrier against external stimuli, such as ultraviolet radiation (UV), xenobiotics, and bacteria. Dermal inflammatory reactions are associated with various skin disorders, including chemical-induced irritation and atopic dermatitis. Modulation of skin inflammatory response is a therapeutic strategy for skin diseases. Here, we synthesized chrysin-derivatives and identified the most potent derivative of Compound 6 (CPD 6). We evaluated its anti-inflammatory ef ...[more]

PMID: 31141897

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Project description:Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine and has been implicated in inflammatory diseases. However, little is known about the regulation of MIF in adipose tissue and its impact on wound healing. The aim of this study was to investigate MIF expression in inflamed adipose and determine its role in inflammatory cell recruitment and wound healing. Adipose tissue was harvested from subcutaneous adipose tissue layers of 24 healthy subjects and from adipose tissue adjacent to acutely inflamed wounds of 21 patients undergoing wound debridement. MIF protein and mRNA expression were measured by ELISA and RT-PCR. Cell-specific MIF expression was visualized by immunohistochemistry. The functional role of MIF in cell recruitment was investigated by a chemotaxis assay and by flow cytometry of labeled macrophages that were injected into Mif-/-and wildtype mice. Wound healing was evaluated by an in vitro scratch assay on human fibroblast monolayers. MIF protein levels of native adipose tissue and supernatants from acutely inflamed wounds were significantly elevated when compared to healthy controls. MIF mRNA expression was increased in acutely inflamed adipose tissue indicating the activation of MIF gene transcription in response to adipose tissue inflammation. MIF is expressed in mature adipocytes and in infiltrated macrophages. Peripheral blood mononuclear cell migration was significantly increased towards supernatants derived from inflamed adipose tissue. This effect was partially abrogated by MIF-neutralizing antibodies. Moreover, when compared to wildtype mice, Mif-/-mice showed reduced infiltration of labeled macrophages into LPS-stimulated epididymal fat pads in vivo. Finally, MIF antibodies partially neutralized the detrimental effect of MIF on fibroblast wound healing. Our results indicate that increased MIF expression and rapid activation of the MIF gene in fat tissue adjacent to acute wound healing disorders may play a role in cell recruitment to the site of inflammation and wound healing.

Dataset Information

Inhibitory Effects of a Novel Chrysin-Derivative, CPD 6, on Acute and Chronic Skin Inflammation.

Publications

Inhibitory Effects of a Novel Chrysin-Derivative, CPD 6, on Acute and Chronic Skin Inflammation.

Similar Datasets

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