ß2-adrenoceptor signaling reduction is involved in the inflammatory response of fibroblast-like synoviocytes from adjuvant-induced arthritic rats.
Inflammopharmacology
; 27(2): 271-279, 2019 Apr.
Article
en En
| MEDLINE
| ID: mdl-29675711
ABSTRACT
OBJECTIVE:
To investigate the effects of ß-AR signaling on fibroblast-like synoviocytes (FLS) from adjuvant-induced arthritis (AA) rats and the partial mechanisms focused on ß-AR desensitization mediated by GRK2 and ß-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 ß-AR agonist isoprenaline (ISO) and the ß2-AR agonist salbutamol on FLS cell viability were detected by CCK8. Cytokines TNF-α, IL-1ß, OPG and RANKL were examined by ELISA. The expression of ß2-AR was detected by immunofluorescence and flow cytometry. The cytomembrane expression and desensitization of ß2-AR, GRK2, and ß-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-1ß, and RANKL secretion, and promoted OPG secretion. ß2-AR mediated the effects of ISO on FLS cell viability. ß2-AR signaling was weaker in AA rats compared to the controls. Elevated GRK2 and ß-arrestin2 in cytomembranes promoted ß2-AR desensitization and may decrease the anti-inflammatory effect of ß2-AR signaling.CONCLUSION:
The activation of ß2-AR signaling exerts its anti-inflammatory activities on FLS. ß2-AR signaling decreased in the AA model, which might be related to the increased membrane expression of GRK2 and ß-arrestin2, and promoted the excessive desensitization of ß2-AR. Decreased ß2-AR signaling may be relevant to the exacerbation of arthritis inflammation.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Artritis Experimental
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Transducción de Señal
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Adyuvantes Farmacéuticos
/
Receptores Adrenérgicos beta 2
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Fibroblastos
/
Sinoviocitos
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Inflamación
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Año:
2019
Tipo del documento:
Article