Email updates

Keep up to date with the latest news and content from Arthritis Research & Therapy and BioMed Central.

Open Access Research article

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

Yohei Kirino1, Mitsuhiro Takeno1, Reikou Watanabe1, Shuji Murakami1, Masayoshi Kobayashi1, Haruko Ideguchi1, Atsushi Ihata1, Shigeru Ohno1, Atsuhisa Ueda1, Nobuhisa Mizuki2 and Yoshiaki Ishigatsubo1*

Author affiliations

1 Department of Internal Medicine and Clinical Immunology, Yokohama City University Graduate School of Medicine, 236-0004, 3-9 Fukuura, Kanazawa-ku, Yokohama, Japan

2 Department of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, 236-0004, 3-9 Fukuura, Kanazawa-ku, Yokohama, Japan

For all author emails, please log on.

Citation and License

Arthritis Research & Therapy 2008, 10:R16  doi:10.1186/ar2367

Published: 31 January 2008

Abstract

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.