HMGB1 Acts in Synergy with Lipopolysaccharide in Activating Rheumatoid Synovial Fibroblasts via p38 MAPK and NF-κB Signaling Pathways
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 p...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2013-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2013/596716 |
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| author | Zheng-Wen He Yang-Hua Qin Zhi-Wei Wang Yan Chen Qian Shen Sheng-Ming Dai |
| author_facet | Zheng-Wen He Yang-Hua Qin Zhi-Wei Wang Yan Chen Qian Shen Sheng-Ming Dai |
| author_sort | Zheng-Wen He |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-7df8984e673d485ab21c60aaef22c21f |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-7df8984e673d485ab21c60aaef22c21f2025-02-03T01:26:08ZengWileyMediators of Inflammation0962-93511466-18612013-01-01201310.1155/2013/596716596716HMGB1 Acts in Synergy with Lipopolysaccharide in Activating Rheumatoid Synovial Fibroblasts via p38 MAPK and NF-κB Signaling PathwaysZheng-Wen He0Yang-Hua Qin1Zhi-Wei Wang2Yan Chen3Qian Shen4Sheng-Ming Dai5Department of Laboratory Diagnosis, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, ChinaDepartment of Laboratory Diagnosis, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, ChinaDepartment of Orthopedics, Changhai Hospital, Second Military Medical University, Shanghai 200433, ChinaDepartment of Laboratory Diagnosis, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, ChinaDepartment of Laboratory Diagnosis, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, ChinaDepartment of Rheumatology & Immunology, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, ChinaSynovial 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.http://dx.doi.org/10.1155/2013/596716 |
| spellingShingle | Zheng-Wen He Yang-Hua Qin Zhi-Wei Wang Yan Chen Qian Shen Sheng-Ming Dai HMGB1 Acts in Synergy with Lipopolysaccharide in Activating Rheumatoid Synovial Fibroblasts via p38 MAPK and NF-κB Signaling Pathways Mediators of Inflammation |
| title | HMGB1 Acts in Synergy with Lipopolysaccharide in Activating Rheumatoid Synovial Fibroblasts via p38 MAPK and NF-κB Signaling Pathways |
| title_full | HMGB1 Acts in Synergy with Lipopolysaccharide in Activating Rheumatoid Synovial Fibroblasts via p38 MAPK and NF-κB Signaling Pathways |
| title_fullStr | HMGB1 Acts in Synergy with Lipopolysaccharide in Activating Rheumatoid Synovial Fibroblasts via p38 MAPK and NF-κB Signaling Pathways |
| title_full_unstemmed | HMGB1 Acts in Synergy with Lipopolysaccharide in Activating Rheumatoid Synovial Fibroblasts via p38 MAPK and NF-κB Signaling Pathways |
| title_short | HMGB1 Acts in Synergy with Lipopolysaccharide in Activating Rheumatoid Synovial Fibroblasts via p38 MAPK and NF-κB Signaling Pathways |
| title_sort | hmgb1 acts in synergy with lipopolysaccharide in activating rheumatoid synovial fibroblasts via p38 mapk and nf κb signaling pathways |
| url | http://dx.doi.org/10.1155/2013/596716 |
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