Blockade of dopamine D1-like receptor signalling protects mice against OVA-induced acute asthma by inhibiting B-cell activating transcription factor signalling and Th17 function

Autor:	Ping Chen, Xudong Xiang, Xiaoying Ji, Zhiguang Zhou, Guyi Wang, Yi Liu, Jinxiu Li, Xiaokun Liu, Shu Zhang, Su-bo Gong, Yu Yang, Ruo-yun Ouyang, Keng Li, Cong-Yi Wang, Li Zhang, Libing Ma
Rok vydání:	2013
Předmět:	Agonist medicine.drug_class Ovalbumin Dopamine Blotting Western Activating transcription factor Enzyme-Linked Immunosorbent Assay Biochemistry Pathogenesis Immunoenzyme Techniques Mice RAR-related orphan receptor gamma medicine Animals RNA Small Interfering Receptor Molecular Biology Transcription factor Lung Cell Proliferation B-Lymphocytes Mice Inbred BALB C business.industry Receptors Dopamine D1 Experimental autoimmune encephalomyelitis Cell Differentiation Cell Biology Benzazepines medicine.disease Flow Cytometry Asthma Blockade Basic-Leucine Zipper Transcription Factors Immunology Acute Disease Th17 Cells Female business Bronchoalveolar Lavage Fluid
Zdroj:	The FEBS journal. 280(23)
ISSN:	1742-4658
Popis:	Previous studies have consistently demonstrated that dopamine D1-like receptor (D1-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 D1-like-R signalling on the pathogenesis of allergic asthma. It was noted that blockade of D1-like-R signalling provided protection for mice against OVA-induced acute asthma. Particularly, treatment of OVA-induced mice with SCH23390, a D1-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 SKF83959, a D1-like-R agonist, displayed the opposite effect. Blockade of D1-like-R signalling impaired Th17 function, as manifested by a significant reduction of Th17 cells in the spleen and bronchoalveolar lavage fluid. Mechanistic studies revealed that D1-like-R signalling enhances B-cell activating transcription factor activity, which then transcribes the expression of RORγt, a Th17 transcription factor; accordingly, D1-like-R signalling regulates Th17 differentiation to promote the development of allergic asthma. Taken together, the data obtained in the present suggest that blockade of D1-like-R signalling could be an effective therapeutic strategy for the prevention and treatment of allergic asthma in clinical practice.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9249c09645fdcd474a6aef66abf042b3 https://pubmed.ncbi.nlm.nih.gov/24112622 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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