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

Immunopharmacol Immunotoxicol. 2019 Feb;41(1):32-39. doi: 10.1080/08923973.2018.1510962. Epub 2019 Feb 6.

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; DNCB; HaCaT cells; atopic dermatitis; mice.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Benzamides / therapeutic use*
  • Cell Line
  • Cyclohexanones / therapeutic use*
  • Cytokines / antagonists & inhibitors
  • Cytokines / immunology
  • Dermatitis, Atopic / immunology
  • Dermatitis, Atopic / pathology
  • Dermatitis, Atopic / prevention & control*
  • Dinitrochlorobenzene
  • Disease Models, Animal
  • Epidermis / drug effects*
  • Epidermis / immunology
  • Epidermis / pathology
  • Female
  • Humans
  • Keratinocytes / drug effects
  • Keratinocytes / immunology
  • Mice, Inbred BALB C
  • NF-kappa B / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Anti-Inflammatory Agents
  • Benzamides
  • Cyclohexanones
  • Cytokines
  • Dinitrochlorobenzene
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • dehydroxymethylepoxyquinomicin