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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2008-01-31

AUTHORS

Yohei Kirino, Mitsuhiro Takeno, Reikou Watanabe, Shuji Murakami, Masayoshi Kobayashi, Haruko Ideguchi, Atsushi Ihata, Shigeru Ohno, Atsuhisa Ueda, Nobuhisa Mizuki, Yoshiaki Ishigatsubo

ABSTRACT

IntroductionToll-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.MethodsThirty-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.ResultsLevels 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.ConclusionThe results suggest that upregulated TLR4 is associated with HO-1 reduction in PBMCs from patients with Behçet's disease, leading to augmented inflammatory responses. More... »

PAGES

r16

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/ar2367

DOI

http://dx.doi.org/10.1186/ar2367

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1002704594

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/18234118


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30 schema:description IntroductionToll-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.MethodsThirty-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.ResultsLevels 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.ConclusionThe results suggest that upregulated TLR4 is associated with HO-1 reduction in PBMCs from patients with Behçet's disease, leading to augmented inflammatory responses.
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37 schema:keywords Behçet's disease
38 HO-1
39 HO-1 expression
40 HO-1 mRNA
41 HO-1 protein levels
42 MethodsThirty-three patients
43 PCR technique
44 TLR
45 TLR2
46 TLR4
47 TLR4 mRNA
48 Toll-like receptor 4 expression
49 activation
50 active Behçet's disease
51 activity
52 association
53 blood mononuclear cells
54 cells
55 control individuals
56 disease
57 disease activity
58 disorders
59 experiments
60 expression
61 expression levels
62 healthy control individuals
63 heme oxygenase
64 heme oxygenase-1
65 immune system
66 individuals
67 inflammatory disorders
68 inflammatory response
69 innate immune system
70 interaction
71 leukocytes
72 levels
73 ligands
74 lipopolysaccharide
75 mRNA
76 mononuclear cells
77 oxygenase
78 oxygenase-1
79 patients
80 peripheral blood mononuclear cells
81 polymorphonuclear leukocytes
82 presence
83 protein
84 protein 60
85 protein levels
86 real-time PCR technique
87 receptor 4 expression
88 receptors
89 reduction
90 response
91 results
92 shock protein 60
93 study
94 system
95 technique
96 triggers activation
97 upregulated TLR4
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