PMID- 22006268
OWN - NLM
STAT- MEDLINE
DCOM- 20120914
LR  - 20211020
IS  - 1529-0131 (Electronic)
IS  - 0004-3591 (Print)
IS  - 0004-3591 (Linking)
VI  - 64
IP  - 4
DP  - 2012 Apr
TI  - FSTL1 promotes arthritis in mice by enhancing inflammatory cytokine/chemokine 
      expression.
PG  - 1082-8
LID - 10.1002/art.33422 [doi]
AB  - OBJECTIVE: FSTL1 is a secreted glycoprotein that exacerbates murine arthritis and 
      is overexpressed in human arthritis. The aim of this study was to determine the 
      mechanism by which FSTL1 promotes arthritis. METHODS: Collagen-induced arthritis 
      was induced in mice hypomorphic for FSTL1, generated with a gene trap-targeted 
      mutant embryonic stem cell line. Arthritis was assessed by measuring paw swelling 
      and using a qualitative arthritis index. Bone marrow-derived mesenchymal stromal 
      cells from hypomorphic mice, as well as mouse stromal ST2 cells transduced with 
      short hairpin RNA to suppress FSTL1 expression, were stimulated with 
      interleukin-1beta (IL-1beta), tumor necrosis factor alpha, and IL-17. The monocyte cell 
      line U937, which does not express FSTL1, was transfected with a plasmid encoding 
      FSTL1 and stimulated with phorbol myristate acetate and lipopolysaccharide. Cell 
      supernatants were assayed for IL-6, IL-8, monocyte chemotactic protein 1 (MCP-1), 
      and FSTL1 by enzyme-linked immunosorbent assay. RESULTS: FSTL1 hypomorphic mice 
      had reduced levels of FSTL1 compared to littermate controls. Following induction 
      of arthritis, a significant correlation was observed between serum FSTL1 levels 
      and both paw swelling and the arthritis index. Similar correlations were observed 
      between the amount of FSTL1 produced by mesenchymal stromal cells, stromal ST2 
      cells, and monocytes and the secretion of IL-6, IL-8, and MCP-1. CONCLUSION: 
      These findings demonstrate that FSTL1 up-regulates proinflammatory mediators 
      important in the pathology of arthritis, and that serum levels of FSTL1 correlate 
      with severity of arthritis. The latter supports the possibility that FSTL1 might 
      be a target for treatment of certain forms of arthritis.
CI  - Copyright (c) 2012 by the American College of Rheumatology.
FAU - Chaly, Yury
AU  - Chaly Y
AD  - Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, 
      University of Pittsburgh, Pittsburgh, Pennsylvania 15224, USA. yury.chaly@chp.edu
FAU - Marinov, Anthony D
AU  - Marinov AD
FAU - Oxburgh, Leif
AU  - Oxburgh L
FAU - Bushnell, Daniel S
AU  - Bushnell DS
FAU - Hirsch, Raphael
AU  - Hirsch R
LA  - eng
GR  - R01-AI-073556/AI/NIAID NIH HHS/United States
GR  - R01 AR056959-04/AR/NIAMS NIH HHS/United States
GR  - R01-AR-056959/AR/NIAMS NIH HHS/United States
GR  - R01 AR056959/AR/NIAMS NIH HHS/United States
GR  - R01 AI073556/AI/NIAID NIH HHS/United States
GR  - R01 AI073556-04/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20111017
PL  - United States
TA  - Arthritis Rheum
JT  - Arthritis and rheumatism
JID - 0370605
RN  - 0 (Chemokines)
RN  - 0 (Cytokines)
RN  - 0 (Follistatin-Related Proteins)
RN  - 0 (Fstl1 protein, mouse)
SB  - IM
MH  - Animals
MH  - Arthritis, Experimental/*metabolism/pathology
MH  - Cell Line
MH  - Chemokines/*metabolism
MH  - Cytokines/*metabolism
MH  - Follistatin-Related Proteins/*metabolism
MH  - Joints/metabolism/pathology
MH  - Mesenchymal Stem Cells/metabolism/pathology
MH  - Mice
MH  - Monocytes/metabolism/pathology
MH  - Severity of Illness Index
PMC - PMC3276726
MID - NIHMS331855
EDAT- 2011/10/19 06:00
MHDA- 2012/09/15 06:00
PMCR- 2013/04/01
CRDT- 2011/10/19 06:00
PHST- 2011/10/19 06:00 [entrez]
PHST- 2011/10/19 06:00 [pubmed]
PHST- 2012/09/15 06:00 [medline]
PHST- 2013/04/01 00:00 [pmc-release]
AID - 10.1002/art.33422 [doi]
PST - ppublish
SO  - Arthritis Rheum. 2012 Apr;64(4):1082-8. doi: 10.1002/art.33422. Epub 2011 Oct 17.