Abstract | INTRODUCTION: High mobility group box-1 ( HMGB1), a typical damage-associated molecular pattern (DAMP) protein, is associated with inflammatory conditions and tissue damage. Our recent study found that circulating HMGB1 levels could reflect the disease activity of antineutrophil cytoplasmic antibody ( ANCA)-associated vasculitis (AAV). The current study aimed to investigate whether HMGB1 participated in ANCA-induced neutrophil activation, which is one of the most important pathogenic aspects in the development of AAV. METHODS: The various effects of HMGB1 in ANCA-induced neutrophil activation were measured. Antagonists for relevant receptors and signaling molecules were employed. RESULTS:
ANCA antigens translocation on neutrophils primed with HMGB1 was significantly higher than non-primed neutrophils. The levels of respiratory burst and degranulation increased significantly in HMGB1-primed neutrophils activated with ANCA-positive IgG, as compared with non-primed neutrophils. Furthermore, blocking Toll-like receptor 4 (TLR4) and receptor for advanced glycation end products (RAGE), rather than TLR2, resulted in a significant decrease in HMGB1-induced ANCA antigens translocation, respiratory burst and degranulation. Similar effects were also found when blocking MyD88 and NF-κB. CONCLUSIONS:
HMGB1 could prime neutrophils by increasing ANCA antigens translocation, and the primed neutrophils could be further induced by ANCA, resulting in the respiratory burst and degranulation. This process is TLR4- and RAGE-dependent through the MyD88/NF-κB pathway.
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Authors | Chen Wang, Huan Wang, Dong-Yuan Chang, Jian Hao, Ming-Hui Zhao, Min Chen |
Journal | Arthritis research & therapy
(Arthritis Res Ther)
Vol. 17
Pg. 64
(Mar 18 2015)
ISSN: 1478-6362 [Electronic] England |
PMID | 25889374
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies, Antineutrophil Cytoplasmic
- HMGB1 Protein
- TLR4 protein, human
- Toll-Like Receptor 4
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Topics |
- Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
(immunology, metabolism, pathology)
- Antibodies, Antineutrophil Cytoplasmic
(biosynthesis, immunology)
- Blotting, Western
- Cells, Cultured
- Enzyme-Linked Immunosorbent Assay
- HMGB1 Protein
(biosynthesis, immunology)
- Humans
- Immunity, Cellular
- Neutrophil Activation
(immunology)
- Neutrophils
(immunology)
- Signal Transduction
- Toll-Like Receptor 4
(biosynthesis, immunology)
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