Association of reduced heme oxygenase-1 with excessive Toll-like receptor 4 expression in peripheral blood mononuclear cells in Behçet's disease

Arthritis Res Ther. 2008;10(1):R16. doi: 10.1186/ar2367. Epub 2008 Jan 31.


Introduction: Toll-like receptors (TLRs) mediate signaling that triggers activation of the innate immune system, whereas heme oxygenase (HO)-1 (an inducible heme-degrading enzyme that is induced by various stresses) suppresses inflammatory responses. We investigated the interaction between TLR and HO-1 in an inflammatory disorder, namely Behçet's disease.

Methods: Thirty-three patients with Behçet's disease and 30 healthy control individuals were included in the study. Expression levels of HO-1, TLR2 and TLR4 mRNA were semiquantitatively analyzed using a real-time PCR technique, and HO-1 protein level was determined by immunoblotting in peripheral blood mononuclear cells (PBMCs) and polymorphonuclear leukocytes. In some experiments, cells were stimulated with lipopolysaccharide or heat shock protein-60; these proteins are known to be ligands for TLR2 and 4.

Results: Levels of expression of HO-1 mRNA were significantly reduced in PBMCs from patients with active Behçet's disease, whereas those of TLR4, but not TLR2, were increased in PBMCs, regardless of disease activity. Moreover, HO-1 expression in PBMCs from patients with Behçet's disease was repressed in the presence of either lipopolysaccharide or heat shock protein-60.

Conclusion: The results suggest that upregulated TLR4 is associated with HO-1 reduction in PBMCs from patients with Behçet's disease, leading to augmented inflammatory responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Behcet Syndrome / blood*
  • Cells, Cultured
  • Chaperonin 60 / pharmacology
  • Computer Systems
  • Female
  • Heme Oxygenase-1 / blood*
  • Heme Oxygenase-1 / genetics
  • Humans
  • Immunoblotting
  • Lipopolysaccharides / pharmacology
  • Male
  • Middle Aged
  • Monocytes / drug effects
  • Monocytes / metabolism*
  • Polymerase Chain Reaction
  • RNA, Messenger / blood
  • Reverse Transcriptase Polymerase Chain Reaction
  • Toll-Like Receptor 2 / genetics
  • Toll-Like Receptor 4 / blood*


  • Chaperonin 60
  • Lipopolysaccharides
  • RNA, Messenger
  • TLR2 protein, human
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Heme Oxygenase-1