Xiaoxue Jiang1, Huan He1, Zhehui Xie1, Huimin Wen1, Xiaoran Li1, Xin Li1, Jun Ma2, Kazuo Umezawa3, Yuyang Zhang1. 1. a School of Life Science and Biopharmaceutics , Shenyang Pharmaceutical University , Shenyang , China. 2. b Department of Research and Development , Shenzhen Wanhe Pharmaceutical Co., Ltd , Shenzhen , China. 3. c Department of Molecular Target Medicine , Aichi Medical University School of Medicine , Nagakute , Japan.
Abstract
Background: Dehydroxymethylepoxyquinomicin (DHMEQ) is a specific and potent inhibitor of nuclear factor-kappa B (NF-κB) and has been shown to possess promising potential as an anti-inflammation including anti-atopic dermatitis (AD)-like skin lesions. Objective: To further evaluate the activity of DHMEQ in vivo modified AD-like lesion model in BALB/c mice and in vitro AD-like lesion cell model in human keratinocytes. Materials and methods: In this study, in vivo modified AD-like lesion model in BALB/c mice was chronically induced by the repetitive and alternative application of 2,4-dinitrochlorobenzene (DNCB) and oxazolone (OX) on ears, and stratum corneum of the ear skin was additionally stripped off with surgical tapes before each challenge with DNCB/OX. Moreover, in vitro AD-like lesion cell model in human keratinocytes (HaCaT) achieved by stimulating HaCaT cells with tumor necrosis factor (TNF)-α plus interferon (IFN)-γ was used to investigate mechanisms of the action. Results: The lesions derived from the stratum corneum-removed AD-like lesion model reaches to peak as well as DHMEQ arrives to its efficacy a week earlier than the data previously obtained from the common AD-like lesion model. Results showed that the drug reduced the ear thickness, epidermal thickness, mast cell infiltration, and gene expressions of interleukin (IL)-4, IL-13, and interferon (IFN)-γ in ear tissues. It significantly inhibited the expression of cytokines IL-6 and IL-1β, chemokines thymus and activation-regulated chemokine (TARC)/CCL17, and macrophage-derived chemokine (MDC)/CCL22 in the stimulated HaCaT cells. Discussion and conclusion: This study indicated that the action of DHMEQ's anti-AD like lesions might be related to its inhibition on NF-κB.
Background: Dehydroxymethylepoxyquinomicin (DHMEQ) is a specific and potent inhibitor of nuclear factor-kappa B (NF-κB) and has been shown to possess promising potential as an anti-inflammation including anti-atopic dermatitis (AD)-like skin lesions. Objective: To further evaluate the activity of DHMEQ in vivo modified AD-like lesion model in BALB/c mice and in vitro AD-like lesion cell model in human keratinocytes. Materials and methods: In this study, in vivo modified AD-like lesion model in BALB/c mice was chronically induced by the repetitive and alternative application of 2,4-dinitrochlorobenzene (DNCB) and oxazolone (OX) on ears, and stratum corneum of the ear skin was additionally stripped off with surgical tapes before each challenge with DNCB/OX. Moreover, in vitro AD-like lesion cell model in human keratinocytes (HaCaT) achieved by stimulating HaCaT cells with tumor necrosis factor (TNF)-α plus interferon (IFN)-γ was used to investigate mechanisms of the action. Results: The lesions derived from the stratum corneum-removed AD-like lesion model reaches to peak as well as DHMEQ arrives to its efficacy a week earlier than the data previously obtained from the common AD-like lesion model. Results showed that the drug reduced the ear thickness, epidermal thickness, mast cell infiltration, and gene expressions of interleukin (IL)-4, IL-13, and interferon (IFN)-γ in ear tissues. It significantly inhibited the expression of cytokines IL-6 and IL-1β, chemokines thymus and activation-regulated chemokine (TARC)/CCL17, and macrophage-derived chemokine (MDC)/CCL22 in the stimulated HaCaT cells. Discussion and conclusion: This study indicated that the action of DHMEQ's anti-AD like lesions might be related to its inhibition on NF-κB.