PMID- 16709864
OWN - NLM
STAT- MEDLINE
DCOM- 20060713
LR  - 20211203
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 176
IP  - 11
DP  - 2006 Jun 1
TI  - Identification of small heat shock protein B8 (HSP22) as a novel TLR4 ligand and 
      potential involvement in the pathogenesis of rheumatoid arthritis.
PG  - 7021-7
AB  - Dendritic cells (DCs) are specialized APCs that can be activated upon pathogen 
      recognition as well as recognition of endogenous ligands, which are released 
      during inflammation and cell stress. The recognition of exogenous and endogenous 
      ligands depends on TLRs, which are abundantly expressed in synovial tissue from 
      rheumatoid arthritis (RA) patients. Furthermore TLR ligands are found to be 
      present in RA serum and synovial fluid and are significantly increased, compared 
      with serum and synovial fluid from healthy volunteers and patients with systemic 
      sclerosis and systemic lupus erythematosus. Identification of novel endogenous 
      TLR ligands might contribute to the elucidation of the role of TLRs in RA and 
      other autoimmune diseases. In this study, we investigated whether five members of 
      the small heat shock protein (HSP) family were involved in TLR4-mediated DC 
      activation and whether these small HSPs were present in RA synovial tissue. In 
      vitro, monocyte-derived DCs were stimulated with recombinant alphaA crystallin, 
      alphaB crystallin, HSP20, HSPB8, and HSP27. Using flow cytometry and multiplex 
      cytokine assays, we showed that both alphaA crystallin and HSPB8 were able to 
      activate DCs and that this activation was TLR4 dependent. Furthermore, Western 
      blot and immunohistochemistry showed that HSPB8 was abundantly expressed in 
      synovial tissue from patients with RA. With these experiments, we identified sHSP 
      alphaA crystallin and HSPB8 as two new endogenous TLR4 ligands from which HSPB8 
      is abundantly expressed in RA synovial tissue. These findings suggest a role for 
      HSPB8 during the inflammatory process in autoimmune diseases such as RA.
FAU - Roelofs, Mieke F
AU  - Roelofs MF
AD  - Department of Rheumatology Research and Advanced Therapeutics, Nijmegen Center 
      for Molecular Life Sciences, The Netherlands. m.roelofs@reuma.umcn.nl
FAU - Boelens, Wilbert C
AU  - Boelens WC
FAU - Joosten, Leo A B
AU  - Joosten LA
FAU - Abdollahi-Roodsaz, Shahla
AU  - Abdollahi-Roodsaz S
FAU - Geurts, Jeroen
AU  - Geurts J
FAU - Wunderink, Liza U
AU  - Wunderink LU
FAU - Schreurs, B Willem
AU  - Schreurs BW
FAU - van den Berg, Wim B
AU  - van den Berg WB
FAU - Radstake, Timothy R D J
AU  - Radstake TR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Cytokines)
RN  - 0 (HSPB8 protein, human)
RN  - 0 (Heat-Shock Proteins)
RN  - 0 (Ligands)
RN  - 0 (Molecular Chaperones)
RN  - 0 (TLR4 protein, human)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (alpha-Crystallin A Chain)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Arthritis, Rheumatoid/*immunology/*metabolism/pathology
MH  - Cell Differentiation/immunology
MH  - Cells, Cultured
MH  - Cytokines/biosynthesis
MH  - Dendritic Cells/cytology/immunology/metabolism
MH  - Heat-Shock Proteins/biosynthesis/metabolism/*physiology
MH  - Humans
MH  - Ligands
MH  - Macrophages, Peritoneal/immunology/metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Knockout
MH  - Molecular Chaperones
MH  - Protein Serine-Threonine Kinases/biosynthesis/metabolism/*physiology
MH  - Synovial Membrane/metabolism
MH  - Toll-Like Receptor 4/deficiency/genetics/*metabolism
MH  - Up-Regulation/immunology
MH  - alpha-Crystallin A Chain/physiology
EDAT- 2006/05/20 09:00
MHDA- 2006/07/14 09:00
CRDT- 2006/05/20 09:00
PHST- 2006/05/20 09:00 [pubmed]
PHST- 2006/07/14 09:00 [medline]
PHST- 2006/05/20 09:00 [entrez]
AID - 176/11/7021 [pii]
AID - 10.4049/jimmunol.176.11.7021 [doi]
PST - ppublish
SO  - J Immunol. 2006 Jun 1;176(11):7021-7. doi: 10.4049/jimmunol.176.11.7021.