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Inflammopharmacology
Published in: Inflammopharmacology 2/2019

01-04-2019 | Original Article

β2-adrenoceptor signaling reduction is involved in the inflammatory response of fibroblast-like synoviocytes from adjuvant-induced arthritic rats

Authors: Huaxun Wu, Jingyu Chen, Chun Wang, Lihua Liu, Yujing Wu, Yunfang Zhang, Aiwu Zhou, Lingling Zhang, Wei Wei

Published in: Inflammopharmacology | Issue 2/2019

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Abstract

Objective

To investigate the effects of β-AR signaling on fibroblast-like synoviocytes (FLS) from adjuvant-induced arthritis (AA) rats and the partial mechanisms focused on β-AR desensitization mediated by GRK2 and β-arrestin2.

Methods

Animals were divided into a control group and an AA model group, and FLSs were cultured. Arthritis index, histopathology of joints, epinephrine (Epi) and norepinephrine (NE) were detected in vivo. The effect of the β-AR agonist isoprenaline (ISO) and the β2-AR agonist salbutamol on FLS cell viability were detected by CCK8. Cytokines TNF-α, IL-1β, OPG and RANKL were examined by ELISA. The expression of β2-AR was detected by immunofluorescence and flow cytometry. The cytomembrane expression and desensitization of β2-AR, GRK2, and β-arrestin2 were measured by flow cytometry and western blot.

Results

The concentration of NE increased to a peak on day 21, which was consistent with the arthritis index. The levels of Epi and NE in synovial tissues were decreased. ISO inhibited FLS cell viability and TNF-α, IL-1β, and RANKL secretion, and promoted OPG secretion. β2-AR mediated the effects of ISO on FLS cell viability. β2-AR signaling was weaker in AA rats compared to the controls. Elevated GRK2 and β-arrestin2 in cytomembranes promoted β2-AR desensitization and may decrease the anti-inflammatory effect of β2-AR signaling.

Conclusion

The activation of β2-AR signaling exerts its anti-inflammatory activities on FLS. β2-AR signaling decreased in the AA model, which might be related to the increased membrane expression of GRK2 and β-arrestin2, and promoted the excessive desensitization of β2-AR. Decreased β2-AR signaling may be relevant to the exacerbation of arthritis inflammation.
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Metadata
Title
β2-adrenoceptor signaling reduction is involved in the inflammatory response of fibroblast-like synoviocytes from adjuvant-induced arthritic rats
Authors
Huaxun Wu
Jingyu Chen
Chun Wang
Lihua Liu
Yujing Wu
Yunfang Zhang
Aiwu Zhou
Lingling Zhang
Wei Wei
Publication date
01-04-2019
Publisher
Springer International Publishing
Published in
Inflammopharmacology / Issue 2/2019
Print ISSN: 0925-4692
Electronic ISSN: 1568-5608
DOI
https://doi.org/10.1007/s10787-018-0477-x

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