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TACE-dependent amphiregulin release is induced by IL-1β and promotes cell invasion in fibroblast-like synoviocytes in rheumatoid arthritis.
- Source :
- Rheumatology; Feb2014, Vol. 53 Issue 2, p260-269, 10p, 1 Color Photograph, 5 Graphs
- Publication Year :
- 2014
-
Abstract
- Objectives. The aims of this study were to investigate the expression of amphiregulin (AREG) and TNF-α-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-1β-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-1β-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-1β, 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-1β induced AREG expression via p38 MAPK, NF-κB, JNK and ERK1/2 signalling pathways and induced TACE expression via PI3K, p38MAPK and NF-κB 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-1β 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-1β-induced AREG release. Our results demonstrate that IL-1β-induced AREG release may be involved in the pathogenesis of RA. [ABSTRACT FROM PUBLISHER]
- Subjects :
- ACADEMIC medical centers
DOSE-response relationship in biochemistry
ENZYME-linked immunosorbent assay
IMMUNOHISTOCHEMISTRY
INTERLEUKINS
POLYMERASE chain reaction
RESEARCH funding
RHEUMATOID arthritis
TUMOR necrosis factors
U-statistics
WESTERN immunoblotting
REVERSE transcriptase polymerase chain reaction
Subjects
Details
- Language :
- English
- ISSN :
- 14620324
- Volume :
- 53
- Issue :
- 2
- Database :
- Complementary Index
- Journal :
- Rheumatology
- Publication Type :
- Academic Journal
- Accession number :
- 93914820
- Full Text :
- https://doi.org/10.1093/rheumatology/ket350