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

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

author email corresponding author email

Arthritis Research & Therapy 2008, 10:R16doi: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.