β2-adrenoceptor signaling reduction in dendritic cells is involved in the inflammatory response in adjuvant-induced arthritic rats

Abstract

Rheumatoid arthritis (RA) is characterized by inflammation of the synovium, which leads to the progressive destruction of cartilage and bone. Adrenoreceptor (AR) signaling may play an important role in modulating dendritic cell (DC), which may be involved in the pathogenesis of RA. We examined the effect of the β-AR agonist isoprenaline (ISO) on DC function, the impact of the β2-AR agonist salbutamol on adjuvant-induced arthritic (AA) rats, and changes in β2-AR signaling in DCs during the course of AA. ISO inhibited the expression of the surface molecules CD86 and MHC-II, inhibited the stimulation of T lymphocyte proliferation by DC and TNF-α secretion, and promoted DC antigen uptake and IL-10 secretion. The effects of ISO on MHC-II expression, DC stimulation of T lymphocyte proliferation, and DC antigen uptake were mediated by β2-AR. Treatment with salbutamol ameliorated the severity of AA and histopathology of the joints and inhibited proliferation of thymus lymphocytes and FLS in vivo. β2-AR signaling was weaker in AA rats compared to the control. Elevated GRK2 and decreased β2-AR expression in DC cytomembranes were observed in AA and may have decreased the anti-inflammatory effect of β2-AR signaling. Decreased β2-AR signaling may be relevant to the exacerbation of arthritis inflammation.

Proinflammatory Cytokines Mediate GPCR Dysfunction

“…Thus, TNFα-induced βAR desensitization mediated by GRK2 in conditions of heart failure is observed to be independent of Gβγ subunits 10 (Fig 1B). Correspondingly, a recent study reported elevated GRK2 and decreased β2AR expression in dendritic cell cytomembranes of adjuvant induced arthritis model 233 further supporting the view that GRK2 function is regulated under conditions of inflammation. Accordingly, treatment of lung epithelial cells with glucocorticoids (anti-inflammatory agent) resulted in significant inhibition of GRK2 expression 234 .…”

TRAF6 regulates the effects of polarized maturation of tolerability: Marrow-derived dendritic cells on collagen-induced arthritis in mice

“…DCs present a two-way immune regulation: i) Ability to capture, process, and present exogenous antigens leading to T-cell differentiation and immune response; and ⅱ) ability of DC to trigger an effective T-cell response and production of self-and foreign antigens. Thus, DCs are important in sustaining the central and peripheral immune tolerance (16)(17)(18)(19).…”

Er Miao San, a traditional Chinese herbal formula, attenuates complete Freund’s adjuvant-induced arthritis in rats by regulating Th17/Treg cells

“…Hind paw volume was measured with a PV-200 volume metre (Chengdu Technology Market Co. Ltd., Chengdu, China) before (base value) and after immunization (days 14, 17, 20, 23, 26, 29 and 32). The polyarthritis index was scored by erythema and joint swelling ranging from 0 to 4, and a maximum arthritic score was set at 16 per animal, as discussed in an earlier study (Wu et al 2016).…”

“…Paraffin sections were stained with haematoxylin and eosin (H&E) and examined microscopically. The severity of arthritis was scored under blinded conditions from 0 to 4 according to synovium hyperplasia, mononuclear cell infiltration, pannus formation, and erosion of articular cartilage and subchondral bone as described previously (Wu et al 2016).…”