Verteporfin inhibits lipopolysaccharide-induced inflammation by multiple functions in RAW 264.7 cells

Toxicol Appl Pharmacol. 2020 Jan 15:387:114852. doi: 10.1016/j.taap.2019.114852. Epub 2019 Dec 5.

Abstract

Inflammation is a physiologic response to damage triggered by infection, injury or chemical irritation. Chronic inflammation produces repeated damage to cells and tissues, which can induce a variety of human diseases including cancer. Verteporfin, an FDA approved drug, is used for the treatment of age-related macular degeneration. The anti-tumor effects of verteporfin have been demonstrated by a number of studies. However, fewer studies focus on the anti-inflammatory functions of this drug. In this study, we investigated the anti-inflammatory effects and potential mechanisms of verteporfin. The classic lipopolysaccharide (LPS)-induced inflammation cell model was used. RAW 264.7 cells were pre-treated with verteporfin or vehicle control, followed by LPS stimulation. Verteporfin inhibited IL-6 and TNF-α at mRNA and protein expression levels. This effect was mediated through inhibition of the NF-κB and JAK/STAT pathways. Finally, verteporfin exhibited an anti-inflammation effect by crosslinking of protein such as NF-κB p65, JAK1, JAK2, STAT1, or STAT3 leading to inflammation. Taken together, these results indicate that verteporfin has the potential to be an effective therapeutic agent against inflammatory diseases.

Keywords: Inflammation; LPS; RAW 264.7; Verteporfin.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use
  • Humans
  • Inflammation / drug therapy*
  • Inflammation / immunology
  • Inflammation Mediators / immunology
  • Inflammation Mediators / metabolism
  • Lipopolysaccharides / immunology
  • Macrophages / drug effects*
  • Macrophages / immunology
  • Macrophages / metabolism
  • Mice
  • RAW 264.7 Cells
  • Signal Transduction / drug effects*
  • Signal Transduction / immunology
  • Verteporfin / pharmacology*
  • Verteporfin / therapeutic use

Substances

  • Anti-Inflammatory Agents
  • Inflammation Mediators
  • Lipopolysaccharides
  • Verteporfin