Litsea japonica Leaf Extract Suppresses Proinflammatory Cytokine Production in Periodontal Ligament Fibroblasts Stimulated with Oral Pathogenic Bacteria or Interleukin-1β

Int J Mol Sci. 2018 Aug 23;19(9):2494. doi: 10.3390/ijms19092494.

Abstract

Periodontal disease, a chronic disease caused by bacterial infection, eventually progresses to severe inflammation and bone loss. Regulating excessive inflammation of inflamed periodontal tissues is critical in treating periodontal diseases. The periodontal ligament (PDL) is primarily a connective tissue attachment between the root and alveolar bone. PDL fibroblasts (PDLFs) produce pro-inflammatory cytokines in response to bacterial infection, which could further adversely affect the tissue and cause bone loss. In this study, we determined the ability of Litsea japonica leaf extract (LJLE) to inhibit pro-inflammatory cytokine production in PDLFs in response to various stimulants. First, we found that LJLE treatment reduced lipopolysaccharide (LPS)-induced pro-inflammatory cytokine (interleukin-6 and interleukin-8) mRNA and protein expression in PDLFs without cytotoxicity. Next, we observed the anti-inflammatory effect of LJLE in PDLFs after infection with various oral bacteria, including Fusobacterium nucleatum, Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia. These anti-inflammatory effects of LJLE were dose-dependent, and the extract was effective following both pretreatment and posttreatment. Moreover, we found that LJLE suppressed the effect of interleukin-1 beta-induced pro-inflammatory cytokine production in PDLFs. Taken together, these results indicate that LJLE has anti-inflammatory activity that could be exploited to prevent and treat human periodontitis by controlling inflammation.

Keywords: IL-6; IL-8; Litsea japonica leaf extract; inflammation; periodontal disease; periodontal ligament.

MeSH terms

  • Adult
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology*
  • Bicuspid / cytology
  • Bicuspid / surgery
  • Cell Survival / drug effects
  • Coculture Techniques
  • Fibroblasts / cytology
  • Fibroblasts / drug effects*
  • Fibroblasts / immunology
  • Fibroblasts / microbiology
  • Fusobacterium nucleatum / chemistry
  • Fusobacterium nucleatum / growth & development
  • Fusobacterium nucleatum / pathogenicity
  • Healthy Volunteers
  • Humans
  • Interleukin-1beta / antagonists & inhibitors*
  • Interleukin-1beta / pharmacology
  • Interleukin-6 / antagonists & inhibitors
  • Interleukin-6 / biosynthesis
  • Interleukin-6 / immunology
  • Interleukin-8 / antagonists & inhibitors
  • Interleukin-8 / biosynthesis
  • Interleukin-8 / immunology
  • Lipopolysaccharides / antagonists & inhibitors*
  • Lipopolysaccharides / pharmacology
  • Litsea / chemistry*
  • Molar / cytology
  • Molar / surgery
  • Periodontal Ligament / cytology
  • Periodontal Ligament / surgery
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Plant Leaves / chemistry
  • Porphyromonas gingivalis / chemistry
  • Porphyromonas gingivalis / growth & development
  • Porphyromonas gingivalis / pathogenicity
  • Primary Cell Culture
  • Tannerella forsythia / chemistry
  • Tannerella forsythia / growth & development
  • Tannerella forsythia / pathogenicity
  • Treponema denticola / chemistry
  • Treponema denticola / growth & development
  • Treponema denticola / pathogenicity

Substances

  • Anti-Inflammatory Agents
  • IL1B protein, human
  • IL6 protein, human
  • Interleukin-1beta
  • Interleukin-6
  • Interleukin-8
  • Lipopolysaccharides
  • Plant Extracts