PMID- 24302816
OWN - NLM
STAT- MEDLINE
DCOM- 20140605
LR  - 20211021
IS  - 1466-1861 (Electronic)
IS  - 0962-9351 (Print)
IS  - 0962-9351 (Linking)
VI  - 2013
DP  - 2013
TI  - HMGB1 acts in synergy with lipopolysaccharide in activating rheumatoid synovial 
      fibroblasts via p38 MAPK and NF-kappaB signaling pathways.
PG  - 596716
LID - 10.1155/2013/596716 [doi]
LID - 596716
AB  - 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 I kappa B. Furthermore, both NF- kappa B 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-kappaB 
      activation.
FAU - He, Zheng-Wen
AU  - He ZW
AD  - Department of Laboratory Diagnosis, Changhai Hospital, Second Military Medical 
      University, 168 Changhai Road, Shanghai 200433, China ; Department of 
      Rheumatology & Immunology, Changhai Hospital, Second Military Medical University, 
      168 Changhai Road, Shanghai 200433, China.
FAU - Qin, Yang-Hua
AU  - Qin YH
FAU - Wang, Zhi-Wei
AU  - Wang ZW
FAU - Chen, Yan
AU  - Chen Y
FAU - Shen, Qian
AU  - Shen Q
FAU - Dai, Sheng-Ming
AU  - Dai SM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131104
PL  - United States
TA  - Mediators Inflamm
JT  - Mediators of inflammation
JID - 9209001
RN  - 0 (BAY 11-7085)
RN  - 0 (HMGB1 Protein)
RN  - 0 (HMGB1 protein, human)
RN  - 0 (IL6 protein, human)
RN  - 0 (Imidazoles)
RN  - 0 (Interleukin-6)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B p50 Subunit)
RN  - 0 (NFKB1 protein, human)
RN  - 0 (Nitriles)
RN  - 0 (Pyridines)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptor for Advanced Glycation End Products)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (Sulfones)
RN  - 0 (TLR4 protein, human)
RN  - 0 (Toll-Like Receptor 4)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 3.4.24.- (MMP13 protein, human)
RN  - EC 3.4.24.- (Matrix Metalloproteinase 13)
RN  - EC 3.4.24.17 (MMP3 protein, human)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - OU13V1EYWQ (SB 203580)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Arthritis, Rheumatoid/*metabolism
MH  - Cell Proliferation
MH  - Fibroblasts/*metabolism
MH  - Gene Expression Regulation
MH  - HMGB1 Protein/*metabolism
MH  - Humans
MH  - Imidazoles/pharmacology
MH  - Interleukin-6/metabolism
MH  - Lipopolysaccharides
MH  - Matrix Metalloproteinase 13/metabolism
MH  - Matrix Metalloproteinase 3/metabolism
MH  - Middle Aged
MH  - NF-kappa B p50 Subunit/*metabolism
MH  - Nitriles/pharmacology
MH  - Phosphorylation
MH  - Pyridines/pharmacology
MH  - RNA, Messenger/metabolism
MH  - Receptor for Advanced Glycation End Products
MH  - Receptors, Immunologic/metabolism
MH  - *Signal Transduction
MH  - Sulfones/pharmacology
MH  - Synovial Membrane/cytology
MH  - Toll-Like Receptor 4/metabolism
MH  - p38 Mitogen-Activated Protein Kinases/*metabolism
PMC - PMC3834620
EDAT- 2013/12/05 06:00
MHDA- 2014/06/06 06:00
PMCR- 2013/11/04
CRDT- 2013/12/05 06:00
PHST- 2013/06/30 00:00 [received]
PHST- 2013/09/05 00:00 [revised]
PHST- 2013/09/21 00:00 [accepted]
PHST- 2013/12/05 06:00 [entrez]
PHST- 2013/12/05 06:00 [pubmed]
PHST- 2014/06/06 06:00 [medline]
PHST- 2013/11/04 00:00 [pmc-release]
AID - 10.1155/2013/596716 [doi]
PST - ppublish
SO  - Mediators Inflamm. 2013;2013:596716. doi: 10.1155/2013/596716. Epub 2013 Nov 4.