3,4,5‑Trihydroxycinnamic acid exerts anti‑inflammatory effects on TNF‑α/IFN‑γ‑stimulated HaCaT cells

Mol Med Rep. 2021 Jul;24(1):509. doi: 10.3892/mmr.2021.12148. Epub 2021 May 13.

Abstract

3,4,5‑Trihydroxycinnamic acid (THCA) exhibits anti‑inflammatory activity in acute or chronic inflammatory disorders, such as acute lung injury and asthma. The present study investigated the anti‑inflammatory activity of THCA in a tumor necrosis factor‑α/interferon‑γ (TI) mixture‑stimulated human keratinocyte cell line. The results of ELISA and reverse transcription‑quantitative PCR revealed that THCA reduced the secretion and mRNA expression levels of interleukin (IL)‑6; IL‑8; thymus and activation‑regulated chemokine; macrophage‑derived chemokine; regulated upon activation, normal T cell expressed and secreted; and monocyte chemoattractant protein‑1 in TI mixture‑stimulated HaCaT cells. In addition, the results of western blot analysis demonstrated that THCA exerted inhibitory activity on the activation of AKT, ERK and nuclear factor‑κB in TI mixture‑stimulated HaCaT cells. Furthermore, THCA upregulated the expression levels of heme oxygenase‑1 and NAD(P)H:quinone oxidoreductase 1, and the activation of nuclear factor erythroid 2‑related factor 2 in HaCaT cells. These results demonstrated that THCA may exhibit anti‑inflammatory activity in activated HaCaT cells.

Keywords: 3; 4; 5‑trihydroxycinnamic acid; atopic dermatitis; inflammatory molecules; nuclear factor‑κB.

MeSH terms

  • ADAM Proteins / genetics
  • ADAM Proteins / metabolism
  • Anti-Inflammatory Agents / pharmacology*
  • Chemokine CCL17 / genetics
  • Chemokine CCL17 / metabolism
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism
  • Chemokine CCL5 / genetics
  • Chemokine CCL5 / metabolism
  • Cinnamates / pharmacology*
  • HaCaT Cells
  • Heme Oxygenase-1 / metabolism
  • Humans
  • Interferon-gamma / pharmacology*
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism
  • Keratinocytes / drug effects*
  • Mitogen-Activated Protein Kinases / metabolism
  • NAD(P)H Dehydrogenase (Quinone) / metabolism
  • NF-E2-Related Factor 2 / metabolism
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism
  • Transcription Factor RelA / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology*
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism

Substances

  • 3,4,5-trihydroxycinnamic acid
  • Anti-Inflammatory Agents
  • CCL17 protein, human
  • CCL2 protein, human
  • CCL5 protein, human
  • CXCL8 protein, human
  • Chemokine CCL17
  • Chemokine CCL2
  • Chemokine CCL5
  • Cinnamates
  • IL6 protein, human
  • Interleukin-6
  • Interleukin-8
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Transcription Factor RelA
  • Tumor Necrosis Factor-alpha
  • Tumor Suppressor Proteins
  • Interferon-gamma
  • HMOX1 protein, human
  • Heme Oxygenase-1
  • NAD(P)H Dehydrogenase (Quinone)
  • NQO1 protein, human
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinases
  • ADAM Proteins
  • ADAM11 protein, human

Grants and funding

The present study was supported by a grant from the Korea Research Institute of Bioscience and Biotechnology Research Initiative Program (grant no. KGM5522113) and the Bio & Medical Technology Development Program of the National Research Foundation (NRF) and the Korean government (MSIT) (grant. no. NRF2020R1A2C2101228).