Dapsone modulates lipopolysaccharide-activated bone marrow cells by inducing cell death and down-regulating tumor necrosis factor-α production

J Vet Sci. 2018 Nov 30;19(6):744-749. doi: 10.4142/jvs.2018.19.6.744.

Abstract

Dapsone, an antibiotic, has been used to cure leprosy. It has been reported that dapsone has anti-inflammatory activity in hosts; however, the anti-inflammatory mechanism of dapsone has not been fully elucidated. The present study investigated the anti-inflammatory effects of dapsone on bone marrow cells (BMs), especially upon exposure to lipopolysaccharide (LPS). We treated BMs with LPS and dapsone, and the treated cells underwent cellular activity assay, flow cytometry analysis, cytokine production assessment, and reactive oxygen species assay. LPS distinctly activated BMs with several characteristics including high cellular activity, granulocyte changes, and tumor necrosis factor alpha (TNF-α) production increases. Interestingly, dapsone modulated the inflammatory cells, including granulocytes in LPS-treated BMs, by inducing cell death. While the percentage of Gr-1 positive cells was 57% in control cells, LPS increased that to 75%, and LPS plus dapsone decreased it to 64%. Furthermore, dapsone decreased the mitochondrial membrane potential of LPS-treated BMs. At a low concentration (25 μg/mL), dapsone significantly decreased the production of TNF-α in LPS-treated BMs by 54%. This study confirmed that dapsone has anti-inflammatory effects on LPS-mediated inflammation via modulation of the number and function of inflammatory cells, providing new and useful information for clinicians and researchers.

Keywords: bone marrow cells; cell death; dapsone; granulocytes; inflammation.

MeSH terms

  • Animals
  • Bone Marrow Cells / drug effects*
  • Bone Marrow Cells / metabolism
  • Cell Death / drug effects*
  • Dapsone / pharmacology*
  • Down-Regulation / drug effects
  • Flow Cytometry
  • Granulocytes / drug effects
  • Granulocytes / metabolism
  • Lipopolysaccharides / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • Reactive Oxygen Species / metabolism
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • Lipopolysaccharides
  • Reactive Oxygen Species
  • Tumor Necrosis Factor-alpha
  • Dapsone