Honokiol possesses potential anti-inflammatory effects on rheumatoid arthritis and GM-CSF can be a target for its treatment

Int J Clin Exp Pathol. 2015 Jul 1;8(7):7929-36. eCollection 2015.

Abstract

Objective: To observe the anti-inflammatory effects of honokiol in primary cultures of peripheral blood mononuclear cells of rheumatoid arthritis patients, the pro-inflammatory cytokines and potential targets were investigated.

Methods: The levels of GM-CSF, IL-1β, TNF-α and IL-8 were determined by ELISA assay. The genes and proteins expression were analyzed by real-time PCR and Western blotting respectively.

Results: The serum IL-1β, TNF-α and GM-CSF levels were 1.76-, 2.16- and 3.57-fold increased in patients with RA as compared to those of control group. Honokiol inhibited the expression levels of IL-1β, TNF-α, GM-CSF and IL-8 in PBMCs with a dose-dependent manner. Measurements obtained from supernatants were positively correlated between TNF-α and IL-1β, moreover, similar results found TNF-α levels positively correlated with GM-CSF and IL-8 activity in the supernatants of PBMCs isolated from RA patients. Furthermore, the mRNA and protein expression of IL-1β, GM-CSF and IL-8 were up-regulated when the PBMCs exposure to TNF-α, however, honokiol treatment significantly reversed the expression of IL-1β, TNF-α and GM-CSF in response to TNF-α with a dose-dependent manner.

Conclusions: This study demonstrates that honokiol could possess potential anti-inflammatory effects and inhibits TNF-α-induced IL-1β, GM-CSF and IL-8 production in PBMCs from rheumatoid arthritis patients.

Keywords: GM-CSF; IL-1β; IL-8; Rheumatoid arthritis; TNF-α.

MeSH terms

  • Adult
  • Aged
  • Anti-Inflammatory Agents / pharmacology*
  • Antirheumatic Agents / pharmacology*
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / genetics
  • Arthritis, Rheumatoid / immunology
  • Biphenyl Compounds / pharmacology*
  • Case-Control Studies
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism*
  • Humans
  • Inflammation Mediators / metabolism*
  • Interleukin-1beta / metabolism
  • Interleukin-8 / metabolism
  • Leukocytes, Mononuclear / drug effects*
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Lignans / pharmacology*
  • Male
  • Middle Aged
  • Primary Cell Culture
  • Signal Transduction / drug effects
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Anti-Inflammatory Agents
  • Antirheumatic Agents
  • Biphenyl Compounds
  • CXCL8 protein, human
  • IL1B protein, human
  • Inflammation Mediators
  • Interleukin-1beta
  • Interleukin-8
  • Lignans
  • Tumor Necrosis Factor-alpha
  • honokiol
  • Granulocyte-Macrophage Colony-Stimulating Factor