PMID- 24196392
OWN - NLM
STAT- MEDLINE
DCOM- 20140527
LR  - 20161125
IS  - 1462-0332 (Electronic)
IS  - 1462-0324 (Linking)
VI  - 53
IP  - 2
DP  - 2014 Feb
TI  - TACE-dependent amphiregulin release is induced by IL-1beta and promotes cell 
      invasion in fibroblast-like synoviocytes in rheumatoid arthritis.
PG  - 260-9
LID - 10.1093/rheumatology/ket350 [doi]
AB  - OBJECTIVES: The aims of this study were to investigate the expression of 
      amphiregulin (AREG) and TNF-alpha-converting enzyme (TACE) in fibroblast-like 
      synoviocytes from humans with RA (FLS-RA) when stimulated with proinflammatory 
      cytokines and to explore whether AREG plays a role in RA. METHODS: The effects of 
      cytokines on the expression of AREG and TACE in FLS-RA were measured by 
      quantitative RT-PCR and western blotting. Blockade of IL-1beta-mediated pathways was 
      used to verify the involvement of intracellular signal pathways in the induction 
      of AREG and TACE. TAPI-1 and TACE short hairpin RNA (shRNA) infection were used 
      to identify the role of TACE in IL-1beta-induced AREG secretion and shedding. 
      AREG-induced production of MMP-1 and cadherin-11 in FLS-RA were measured by ELISA 
      or western blotting. The effect of AREG on FLS-RA invasion was examined using a 
      Transwell invasion assay. RESULTS: IL-1beta, but not other tested cytokines, 
      increased the expressions of AREG mRNA and protein in a dose-responsive and 
      time-dependent manner in FLS-RA. IL-1beta induced AREG expression via p38 MAPK, 
      NF-kappaB, JNK and ERK1/2 signalling pathways and induced TACE expression via PI3K, 
      p38MAPK and NF-kappaB signalling pathways in FLS-RA. TACE mediated AREG secretion and 
      shedding. EGFR (ErbB1) and Her-2 (ErbB2) were expressed in FLS-RA, and AREG 
      increased MMP-1 and cadherin-11 expression in FLS-RA. AREG promoted the FLS-RA 
      invasion ability. CONCLUSION: AREG and TACE expression were up-regulated by IL-1beta 
      and their activations on FLS-RA lead to the matrix degradation by inducing MMP-1 
      and cadherin-11 production. TACE activity is necessary for IL-1beta-induced AREG 
      release. Our results demonstrate that IL-1beta-induced AREG release may be involved 
      in the pathogenesis of RA.
FAU - Liu, Fei-Lan
AU  - Liu FL
AD  - Rheumatology/Immunology/Allergy, Tri-Service General Hospital, 325 Cheng-Kung 
      Road, Section 2, Neihu 114, Taipei, Taiwan, Republic of China. 
      ming0503@ms3.hinet.net.
FAU - Wu, Cheng-Chi
AU  - Wu CC
FAU - Chang, Deh-Ming
AU  - Chang DM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131106
PL  - England
TA  - Rheumatology (Oxford)
JT  - Rheumatology (Oxford, England)
JID - 100883501
RN  - 0 (AREG protein, human)
RN  - 0 (Amphiregulin)
RN  - 0 (Cadherins)
RN  - 0 (EGF Family of Proteins)
RN  - 0 (Glycoproteins)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Interleukin-1beta)
RN  - 0 (NF-kappa B)
RN  - 156621-71-5 (osteoblast cadherin)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 3.4.24.- (ADAM Proteins)
RN  - EC 3.4.24.7 (Matrix Metalloproteinase 1)
RN  - EC 3.4.24.86 (ADAM17 Protein)
RN  - EC 3.4.24.86 (ADAM17 protein, human)
SB  - IM
MH  - ADAM Proteins/*metabolism
MH  - ADAM17 Protein
MH  - Amphiregulin
MH  - Arthritis, Rheumatoid/*metabolism/pathology
MH  - Cadherins/metabolism
MH  - Cell Movement/drug effects
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - EGF Family of Proteins
MH  - Fibroblasts/drug effects/*metabolism/pathology
MH  - Glycoproteins/biosynthesis/*metabolism
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins/biosynthesis/*metabolism
MH  - Interleukin-1beta/*pharmacology
MH  - MAP Kinase Signaling System/physiology
MH  - Matrix Metalloproteinase 1/metabolism
MH  - NF-kappa B/metabolism
MH  - Synovial Membrane/drug effects/*metabolism/pathology
MH  - Time Factors
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
OTO - NOTNLM
OT  - IL-1beta
OT  - amphiregulin
OT  - fibroblast-like synoviocyte
OT  - rheumatoid arthritis
EDAT- 2013/11/08 06:00
MHDA- 2014/05/28 06:00
CRDT- 2013/11/08 06:00
PHST- 2013/11/08 06:00 [entrez]
PHST- 2013/11/08 06:00 [pubmed]
PHST- 2014/05/28 06:00 [medline]
AID - ket350 [pii]
AID - 10.1093/rheumatology/ket350 [doi]
PST - ppublish
SO  - Rheumatology (Oxford). 2014 Feb;53(2):260-9. doi: 10.1093/rheumatology/ket350. 
      Epub 2013 Nov 6.