Dehydroxymethylepoxyquinomicin suppresses atopic dermatitis-like lesions in a stratum corneum-removed murine model through NF-κB inhibition

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.

Keywords:

• DHMEQ
• atopic dermatitis
• DNCB
• mice
• HaCaT cells

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This study was supported in part by National Key Programs in Science and Technology-Discovery and Development of New Drugs with High Clinical Impact (No. 2012ZX09103101-004), Guangdong Provincial Programs for Achieving Core Technological Breakthroughs in Strategic Emerging Industries (No. 2012A080800010), and Shenzhen Municipal Programs for the Research and Development of Technologies (Three Key Industries) (No. JSA201105090126A).