In:
The FEBS Journal, Wiley, Vol. 280, No. 23 ( 2013-12), p. 6262-6273
Abstract:
Previous studies have consistently demonstrated that dopamine D 1‐like receptor ( D 1‐like‐ R ) signalling is implicated in the pathogenesis of experimental autoimmune encephalomyelitis and type I diabetes. Given that allergic asthma shares certain disease aetiology similarities with autoimmune diseases, we conducted studies in OVA ‐induced mice aiming to address the impact of D 1‐like‐ R signalling on the pathogenesis of allergic asthma. It was noted that blockade of D 1‐like‐ R signalling provided protection for mice against OVA ‐induced acute asthma. Particularly, treatment of OVA ‐induced mice with SCH 23390, a D 1‐like‐ R antagonist, significantly attenuated inflammatory infiltration in the airways along with repressed goblet cell hyperplasia and mucus production, as well as airway resistance. By contrast, administration of SKF 83959, a D 1‐like‐ R agonist, displayed the opposite effect. Blockade of D 1‐like‐ R signalling impaired T h17 function, as manifested by a significant reduction of T h17 cells in the spleen and bronchoalveolar lavage fluid. Mechanistic studies revealed that D 1‐like‐ R signalling enhances B ‐cell activating transcription factor activity, which then transcribes the expression of ROR γt, a T h17 transcription factor; accordingly, D 1‐like‐ R signalling regulates T h17 differentiation to promote the development of allergic asthma. Taken together, the data obtained in the present suggest that blockade of D 1‐like‐ R signalling could be an effective therapeutic strategy for the prevention and treatment of allergic asthma in clinical practice.
Type of Medium:
Online Resource
ISSN:
1742-464X
,
1742-4658
DOI:
10.1111/febs.2013.280.issue-23
Language:
English
Publisher:
Wiley
Publication Date:
2013
detail.hit.zdb_id:
2172518-4
SSG:
12
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