Development of Imiquimod-induced HaCaT-THP-1 co-culture for modeling of psoriasis

Eur J Pharm Sci. 2024 Sep 1:200:106846. doi: 10.1016/j.ejps.2024.106846. Epub 2024 Jul 5.

Abstract

Psoriasis is one of the most prevalent and chronic inflammatory disease of the skin, associated with disrupted barrier function. Currently, a widely accepted, generally usable cell culture model has not been developed yet. In the present work, we aimed to establish a co-culture model with human keratinocyte (HaCaT) and human monocyte cells (THP-1) induced by Imiquimod (IMQ), which acts on the TLR7 receptor. The role of TLR7 expressed on THP-1 cells was confirmed by immunofluorescence staining of NF-κB activation. Chloroquine (CH) was used as a receptor inhibitor, in the presence or absence of which the NF-κB pathway was activated. We determined the most effective proliferation-stimulating IMQ concentration by RTCA method and the hyperproliferative effect was investigated by wound-healing test. The effect of IMQ was compared with the effects of the anthocyanin (AC) components from the anti-inflammatory sour cherry extract that we have already studied. We found that IMQ significantly increased the migration rate however, the combined treatment resulted in a decreased migration rate compared to the IMQ treatment alone. Inflammatory cytokines were measured from the supernatant of co-culture by ELISA. During the development of the co-culture intended to model psoriasis, we confirmed the induction effect of IMQ and in the case of AC treatment, we supported the stabilizing effect of the barrier.

Keywords: Anthocyanin; Chloroquine; Co-culture; HaCaT; Imiquimod; Psoriasis; THP-1.

MeSH terms

  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Coculture Techniques*
  • Cytokines / metabolism
  • HaCaT Cells
  • Humans
  • Imiquimod*
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism
  • Models, Biological
  • NF-kappa B / metabolism
  • Psoriasis* / drug therapy
  • Psoriasis* / metabolism
  • THP-1 Cells
  • Toll-Like Receptor 7 / metabolism

Substances

  • Imiquimod
  • Cytokines
  • NF-kappa B
  • Toll-Like Receptor 7
  • TLR7 protein, human