Apamin inhibits TNF-α- and IFN-γ-induced inflammatory cytokines and chemokines via suppressions of NF-κB signaling pathway and STAT in human keratinocytes

Pharmacol Rep. 2017 Oct;69(5):1030-1035. doi: 10.1016/j.pharep.2017.04.006. Epub 2017 Apr 18.

Abstract

Background: Atopic dermatitis (AD) is identified by an increase in infiltrations of several inflammatory cells including type 2 helper (Th2) lymphocytes. Th2-related chemokines such as thymus and activation-regulated chemokine (TARC/CCL17) and macrophage-derived chemokine (MDC/CCL22), and pro-inflammatory cytokines including interleukin (IL)-1β and IL-6 are considered to play a crucial role in AD. Tumor necrosis factor (TNF)-α- and interferon (IFN)-γ induce the inflammatory condition through production of TARC, MDC, IL-1β and IL-6, and activations of related transcription factors, such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and signal transducer and activator of transcription (STAT) in keratinocytes. Apamin, a peptide component of bee venom, has been reported its beneficial activities in various diseases. However, anti-inflammatory effects of apamin on inflammatory condition in keratinocytes have not been explored. Therefore, the present study aimed to demonstrate the anti-inflammatory effect of apamin on TNF-α- and IFN-γ-induced inflammatory condition in keratinocytes.

Methods: HaCaT was used as human keratinocytes cell line. Cell Counting Kit-8 was performed to measure a cytotoxicity of apamin. The effects of apamin on TNF-α-/IFN-γ-induced inflammatory condition were determined by real-time PCR and Western blot analysis. Further, NF-κB signaling pathways, STAT1, and STAT3 were analyzed by Western blot and immunofluorescence.

Results: Apamin ameliorated the inflammatory condition through suppression of Th2-related chemokines and pro-inflammatory cytokines. Further, apamin down-regulated the activations of NF-κB signaling pathways and STATs in HaCaT cells.

Conclusions: These results suggest that apamin has therapeutic effect on AD through improvement of inflammatory condition.

Keywords: Apamin; Atopic dermatitis; NF-κB; STAT; Type 2 helper T lymphocyte chemokine.

MeSH terms

  • Apamin / pharmacology*
  • Cell Line
  • Cell Survival / drug effects
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Cytokines / pharmacology
  • Gene Expression Regulation / drug effects*
  • Humans
  • Interferon-gamma / pharmacology*
  • Keratinocytes / drug effects*
  • Keratinocytes / metabolism
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • STAT Transcription Factors / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology*

Substances

  • Cytokines
  • NF-kappa B
  • STAT Transcription Factors
  • Tumor Necrosis Factor-alpha
  • Apamin
  • Interferon-gamma