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Published in: Inflammation Research 5/2014

01-05-2014 | Original Research Paper

Activated macrophage-like synoviocytes are resistant to endoplasmic reticulum stress-induced apoptosis in antigen-induced arthritis

Authors: Li-Jie Feng, Tong-Cui Jiang, Cheng-Yue Zhou, Chang-Liang Yu, Yu-Jun Shen, Jun Li, Yu-Xian Shen

Published in: Inflammation Research | Issue 5/2014

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Abstract

Objective

To explore the characteristic expression of endoplasmic reticulum (ER) stress protein in antigen-induced arthritis models and the role of ER stress in arthritis.

Methods

Effective animal models of rheumatoid arthritis in rabbits and rats were induced by methylated bovine serum albumin and Freund’s complete adjuvant. Pathological changes were assessed by magnetic resonance imaging and histological analysis. The expression and localization of ER stress proteins in synovium and peritoneal macrophages (PMΦ) were analyzed by double immunofluorescence staining. RT-PCR was performed to detect mRNA expression of ER stress-related genes. Tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) levels in synoviocytes were measured by RT-PCR and radioimmunoassay.

Results

We found that the ER stress marker BiP was highly up-regulated in arthritis synovium and extensively expressed in fibroblast-like synoviocytes (FLS) and macrophage-like synoviocytes (MLS). The expression of the pro-apoptotic factor CHOP/GADD153 was slightly elevated in inflammatory synovium and mainly localized in FLS, but insignificant in MLS. Unexpectedly, increased expression of CHOP was observed in PMΦ in arthritis rats. Likewise, cleaved caspase-3 was rarely expressed in MLS. In addition, induction of ER stress by tunicamycin resulted in significantly increased expression of pro-inflammatory molecules such as IL-1β and TNF-α in cultured inflammatory FLS.

Conclusion

Differential activation of the ER stress proteins in synovium MLS may contribute to the resistance of synoviocytes to ER stress-induced apoptosis. Furthermore, ER stress is a potential mediator of arthritis inflammation.
Appendix
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Metadata
Title
Activated macrophage-like synoviocytes are resistant to endoplasmic reticulum stress-induced apoptosis in antigen-induced arthritis
Authors
Li-Jie Feng
Tong-Cui Jiang
Cheng-Yue Zhou
Chang-Liang Yu
Yu-Jun Shen
Jun Li
Yu-Xian Shen
Publication date
01-05-2014
Publisher
Springer Basel
Published in
Inflammation Research / Issue 5/2014
Print ISSN: 1023-3830
Electronic ISSN: 1420-908X
DOI
https://doi.org/10.1007/s00011-013-0705-1

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