HMGB1 Acts in Synergy with Lipopolysaccharide in Activating Rheumatoid Synovial Fibroblasts via p38 MAPK and NF-κB Signaling Pathways
Joint Authors
He, Zheng-Wen
Shen, Qian
Chen, Yan
Qin, Yang-Hua
Dai, Sheng-Ming
Wang, Zhi-Wei
Source
Issue
Vol. 2013, Issue 2013 (31 Dec. 2013), pp.1-10, 10 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2013-11-04
Country of Publication
Egypt
No. of Pages
10
Main Subjects
Abstract EN
Synovial fibroblasts (SF) play a central role in the inflammatory and destructive process in rheumatoid arthritis (RA).
High-mobility group box chromosomal protein 1 (HMGB1) or lipopolysaccharide (LPS) alone failed to induce significant changes in proliferation of cultured SF from RA patients, but premixed HMGB1 with LPS (HMGB1-LPS) significantly facilitated SF proliferation.
HMGB1 alone failed to induce IL-6, MMP-3, and MMP-13 production in cultured SF but greatly enhanced LPS-induced expression of IL-6, MMP-3, and MMP-13 at both mRNA and protein levels.
HMGB1-LPS synergistically upregulated TLR4 and receptor for advanced glycation endproducts (RAGE) expression on the surface of SF.
Both blockers of TLR4 and RAGE significantly inhibited the synergistic effects of HMGB1-LPS on the production of IL-6 and MMPs, but blocking antibodies to TLR2 failed.
HMGB1-LPS synergistically increased intracellular levels of phosphorylated p38 and phosphorylated IκB.
Furthermore, both NF-κB inhibitor Bay11-7085 and p38 inhibitor SB203580 significantly suppressed the enhanced production of IL-6 and MMPs induced by HMGB1-LPS.
In conclusion, HMGB1 acts in synergy with LPS to upregulate TLR4 and RAGE expression on the surface of SF in RA and then to augment IL-6, MMP-3, and MMP-13 production, which depends on p38 MAPK and NF-κB activation.
American Psychological Association (APA)
He, Zheng-Wen& Qin, Yang-Hua& Wang, Zhi-Wei& Chen, Yan& Shen, Qian& Dai, Sheng-Ming. 2013. HMGB1 Acts in Synergy with Lipopolysaccharide in Activating Rheumatoid Synovial Fibroblasts via p38 MAPK and NF-κB Signaling Pathways. Mediators of Inflammation،Vol. 2013, no. 2013, pp.1-10.
https://search.emarefa.net/detail/BIM-483827
Modern Language Association (MLA)
He, Zheng-Wen…[et al.]. HMGB1 Acts in Synergy with Lipopolysaccharide in Activating Rheumatoid Synovial Fibroblasts via p38 MAPK and NF-κB Signaling Pathways. Mediators of Inflammation No. 2013 (2013), pp.1-10.
https://search.emarefa.net/detail/BIM-483827
American Medical Association (AMA)
He, Zheng-Wen& Qin, Yang-Hua& Wang, Zhi-Wei& Chen, Yan& Shen, Qian& Dai, Sheng-Ming. HMGB1 Acts in Synergy with Lipopolysaccharide in Activating Rheumatoid Synovial Fibroblasts via p38 MAPK and NF-κB Signaling Pathways. Mediators of Inflammation. 2013. Vol. 2013, no. 2013, pp.1-10.
https://search.emarefa.net/detail/BIM-483827
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-483827