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

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.

• Authors: Huaxun Wu, Jingyu Chen, Chun Wang, Lihua Liu, Yujing Wu, Yunfang Zhang, Aiwu Zhou, Lingling Zhang, Wei Wei
• Journal: Inflammopharmacology (Inflammopharmacology) Vol. 27 Issue 2 Pg. 271-279 (Apr 2019) ISSN: 1568-5608 [Electronic] Switzerland
• PMID: 29675711 (Publication Type: Journal Article)

Chemical References

• Adjuvants, Pharmaceutic
• Cytokines
• Interleukin-1beta
• RANK Ligand
• Receptors, Adrenergic, beta-2
• Tumor Necrosis Factor-alpha
• Norepinephrine
• Epinephrine

Topics

• Adjuvants, Pharmaceutic (adverse effects, analysis)
• Animals
• Arthritis, Experimental (chemically induced, metabolism)
• Cell Survival (physiology)
• Cells, Cultured
• Cytokines (metabolism)
• Epinephrine (metabolism)
• Fibroblasts (metabolism)
• Inflammation (metabolism)
• Interleukin-1beta (metabolism)
• Male
• Norepinephrine (metabolism)
• RANK Ligand (metabolism)
• Rats
• Rats, Sprague-Dawley
• Receptors, Adrenergic, beta-2 (metabolism)
• Signal Transduction (physiology)
• Synoviocytes (metabolism)
• Tumor Necrosis Factor-alpha (metabolism)