PMID- 22247344
OWN - NLM
STAT- MEDLINE
DCOM- 20120726
LR  - 20220409
IS  - 1499-2752 (Electronic)
IS  - 0315-162X (Linking)
VI  - 39
IP  - 3
DP  - 2012 Mar
TI  - Interferon-gamma contributes to HLA-B27-associated unfolded protein response in 
      spondyloarthropathies.
PG  - 574-82
LID - 10.3899/jrheum.101257 [doi]
AB  - OBJECTIVE: HLA-B27 positivity strongly influences the susceptibility to and 
      phenotype of spondyloarthropathies (SpA). This study was designed to screen 
      factors that activate the promoter of HLA-B27 in U937 cells, and to assess 
      whether these promoter-activating factors induce the unfolded protein response 
      (UPR) in HLA-B27-expressing cells. METHODS: Cytometric Bead Array, flow 
      cytometry, and real-time polymerase chain reaction were used to detect the 
      expression of cytokines and UPR-associated proteins in peripheral blood and 
      synovial fluid of patients with SpA. The HLA-B27 promotor transfectant was 
      incubated separately with cytokines and Toll-like receptor ligands. After 
      interferon-gamma (IFN-gamma) stimulation, expressions of GRP78, CHOP, and XBP-1 were 
      tested in HLA-B27-expressing U937 cells and peripheral blood mononuclear cell 
      (PBMC) of patients with ankylosing spondylitis (AS). (Clinical trial registration 
      no. ChiCTR-OCC-11001565) RESULTS: Expressions of GRP78, CHOP, and XBP-1 in 
      monocytes/macrophages of SpA peripheral blood and synovial fluid were higher than 
      those in healthy controls and patients with osteoarthritis (OA) (p < 0.05). Tumor 
      necrosis factor-alpha (TNF-alpha) and IFN-alpha, IFN-ss, and IFN-gamma were found to have 
      activated the HLA-B27 promoter in the U937 cell line (p < 0.05). Following 
      stimulation with IFN-gamma, the expressions of GRP78, CHOP and XBP-1 in 
      HLA-B27-transfected U937 cells and PBMC of HLA-B27-positive AS patients were more 
      intense than those in A2-U937 cells, HLA-B27-negative AS patients, or healthy 
      controls (p < 0.05). CONCLUSION: Expressions of GRP78, CHOP, and XBP-1 were 
      higher in monocytes/macrophages of patients with SpA than those in both OA 
      patients and healthy controls, suggesting that UPR may participate in the 
      pathogenesis of SpA. TNF-alpha and IFN-alpha, IFN-ss, and IFN-gamma significantly activated 
      HLA-B27 promoter in the U937 cell line, and IFN-gamma, the strongest activating 
      factor, may induce the UPR in HLA-B27-expressing cells.
FAU - Feng, Yuan
AU  - Feng Y
AD  - Department of Clinical Immunology, State Key Discipline of Cell Biology, Xijing 
      Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
FAU - Ding, Jin
AU  - Ding J
FAU - Fan, Chun Mei
AU  - Fan CM
FAU - Zhu, Ping
AU  - Zhu P
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20120115
PL  - Canada
TA  - J Rheumatol
JT  - The Journal of rheumatology
JID - 7501984
RN  - 0 (Cytokines)
RN  - 0 (DDIT3 protein, human)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Endoplasmic Reticulum Chaperone BiP)
RN  - 0 (HLA-B27 Antigen)
RN  - 0 (HSPA5 protein, human)
RN  - 0 (Heat-Shock Proteins)
RN  - 0 (Regulatory Factor X Transcription Factors)
RN  - 0 (Transcription Factors)
RN  - 0 (X-Box Binding Protein 1)
RN  - 0 (XBP1 protein, human)
RN  - 147336-12-7 (Transcription Factor CHOP)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
EIN - J Rheumatol. 2013 Sep;40(9):1634
MH  - Adult
MH  - Aged
MH  - Arthritis, Psoriatic/metabolism/pathology
MH  - Arthritis, Reactive/metabolism/pathology
MH  - Cytokines/pharmacology
MH  - DNA-Binding Proteins/metabolism
MH  - Endoplasmic Reticulum Chaperone BiP
MH  - Female
MH  - HLA-B27 Antigen/*metabolism
MH  - Heat-Shock Proteins/metabolism
MH  - Humans
MH  - Interferon-gamma/*pharmacology
MH  - Macrophages/drug effects/*metabolism/pathology
MH  - Male
MH  - Middle Aged
MH  - Monocytes/drug effects/*metabolism/pathology
MH  - Osteoarthritis/metabolism/pathology
MH  - Regulatory Factor X Transcription Factors
MH  - Spondylarthropathies/*metabolism/pathology
MH  - Spondylitis, Ankylosing/metabolism/pathology
MH  - Transcription Factor CHOP/metabolism
MH  - Transcription Factors/metabolism
MH  - U937 Cells
MH  - Unfolded Protein Response/*drug effects
MH  - X-Box Binding Protein 1
EDAT- 2012/01/17 06:00
MHDA- 2012/07/27 06:00
CRDT- 2012/01/17 06:00
PHST- 2012/01/17 06:00 [entrez]
PHST- 2012/01/17 06:00 [pubmed]
PHST- 2012/07/27 06:00 [medline]
AID - jrheum.101257 [pii]
AID - 10.3899/jrheum.101257 [doi]
PST - ppublish
SO  - J Rheumatol. 2012 Mar;39(3):574-82. doi: 10.3899/jrheum.101257. Epub 2012 Jan 15.