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

Authors: Kirino, Y  Takeno, M  Watanabe, R  Murakami, S  Kobayashi, M  Ideguchi, H  Ihata, A  Ohno, S  Ueda, A  Mizuki, N  Ishigatsubo, Y 
Citation: Kirino Y, etal., Arthritis Res Ther. 2008;10(1):R16. doi: 10.1186/ar2367. Epub 2008 Jan 31.
Pubmed: (View Article at PubMed) PMID:18234118
DOI: Full-text: DOI:10.1186/ar2367

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 Behcet's disease. METHODS: Thirty-three patients with Behcet'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 Behcet'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 Behcet'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 Behcet's disease, leading to augmented inflammatory responses.

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CRRD ID: 7777175
Created: 2014-01-07
Species: All species
Last Modified: 2014-01-07
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.