Inhibitory effect of 5, 6-dihydroergosteol-glucoside on atopic dermatitis-like skin lesions via suppression of NF-κB and STAT activation. Issue 3 (September 2015)

• Record Type: Journal Article
• Authors: Jung, Mira; Lee, Tae Hoon; Oh, Hyun Jeoung; Kim, Hakwon; Son, Youngsook; Lee, Eunjoo H.; Kim, Jiyoung
• Is Part Of: Journal of dermatological science. Volume 79:Issue 3(2015:Sep.)
• Page Start: 252
• Page End: 261
• Publication Date: 2015-09
• Subjects: 5, 6-Dihydroergosterol-glucoside -- Atopic dermatitis -- Thymus and activation-regulated -- chemokine -- Macrophage-derived chemokine -- NF-κB -- STAT; Dermatology -- Periodicals; Skin Diseases -- Periodicals; Dermatologie -- Périodiques; 616.5005
• DOI: 10.1016/j.jdermsci.2015.06.005
• Languages: English
• ISSNs: 0923-1811

Abstract

Highlights: DHE-Glc attenuates AD-like skin inflammatory symptoms in mice. DHE-Glc suppresses TNF-α/IFN-γ induced TARC and MDC in HaCaT keratinocytes. DHE-Glc inhibits phosphorylation of p38 and JAK2 in TNF-α/IFN-γ induced HaCaT. DHE-Glc suppresses NF-κB and STAT1 activation by TNF-α/IFN-γ in HaCaT. DHE-Glc attenuates skin inflammatory response in vitro and in vivo. Abstract: Background: Atopic dermatitis (AD) is a Th2-type disease. Keratinocytes, a major type in the skin, produce Th2 chemokines such as thymus and activation-regulated chemokine (TARC)/CCL17 and macrophage-derived chemokine (MDC)/CCL22, which play pivotal roles in the development of Th2-dominant inflammatory skin diseases. Recently, it was reported that 5, 6-dihydroergosterol-glucoside (DHE-Glc) was synthesized and exhibited strong anti-inflammatory activity. Objective: We aimed to investigate the effects of DHE-Glc, a synthetic molecule derived from ergosterol, on AD-like skin lesions induced by 2, 4-dinitrochlorobenzene (DNCB) in mice and to elucidate the effects of DHE-Glc on TNF-α/IFN-γ-induced production of CCL17 and CCL22 in human keratinocytes (HaCaTs) and DNCB induced skin inflammation mice model. Method: Mice were sensitized and challenged on the skin of their backs with DNCB. At 30–60 days after sensitization, mice were treated with cutaneous administration of DHE-Glc by skin smear. HaCaT cells were used to evaluate the effects of DHE-Glc on production of CCL17 and CCL22 and investigate mechanisms of action by RT-PCR, ELISA, Western blot, and reporter assays. Result: Topical administration of DHE-Glc attenuated AD-like skin inflammatory symptoms. DHE-Glc decreased infiltration of epidermal eosinophils and mast cells, and reduced levels of IgE, histamine, and mRNA expression and protein levels of CCL17/CCL22 in the plasma of DNCB-treated animals. In addition, DHE-Glc suppressed TNF-α/IFN-γ-induced expression of the Th2 chemokines CCL17 and CCL22 by inhibiting NF-κB and STAT activation in TNF-α/IFN-γ-induced HaCaT cells. Conclusion: DHE-Glc improved AD-like skin inflammatory symptoms on the backs of DNCB-induced mice, partly by suppressing production of Th2 chemokines, CCL17 and CCL22 in inflamed skin. Therefore, DHE-Glc is a potential therapeutic agent for skin inflammatory diseases such as AD.