Effect of P2X4R on airway inflammation and airway remodeling in allergic airway challenge in mice.

Abstract

P2X4 receptor (P2X4R) is the most widely expressed subtype of the P2XRs in the purinergic receptor family. Adenosine triphosphate (ATP), a ligand for this receptor, has been implicated in the pathogenesis of asthma. ATP‑P2X4R signaling is involved in pulmonary vascular remodeling, and in the proliferation and differentiation of airway and alveolar epithelial cell lines. However, the role of P2X4R in asthma remains to be elucidated. This aim of the present study was to investigate the effects of P2X4R in a murine experimental asthma model. The asthmatic model was established by the inhalation of ovalbumin (OVA) in BALB/c mice. The mice were treated with P2X4R‑specific agonists and antagonists to investigate the role of this receptor in vivo. Pathological changes in the bronchi and lung tissues were examined using hematoxylin and eosin staining, Masson's trichrome staining and Alcian blue staining. The inflammatory cells in the bronchoalveolar lavage fluid were counted, and the expression levels of P2X4R, α‑smooth muscle actin (α‑SMA) and proliferating cell nuclear antigen (PCNA) were detected using western blotting. In the OVA‑challenged mice, inflammation, infiltration, collagen deposition, mucus production, and the expression levels of P2X4R and PCNA were all increased; however, the expression of α‑SMA was decreased, compared with the mice in the control group. Whereas treatment with the P2X4R agonist, ATP, enhanced the allergic reaction, treatment with the P2X4R antagonist, 5‑BDBD, attenuated the allergic reaction. The results suggested that ATP‑P2X4R signaling may not only contribute to airway inflammation, but it may also contribute to airway remodeling in allergic asthma in mice.

• Authors: Hongxia Chen, Qingqing Xia, Xiaoqian Feng, Fangyuan Cao, Hang Yu, Yinli Song, Xiuqin Ni
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 13 Issue 1 Pg. 697-704 (Jan 2016) ISSN: 1791-3004 [Electronic] Greece
• PMID: 26648454 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Actins
• Proliferating Cell Nuclear Antigen
• Receptors, Purinergic P2X4
• alpha-smooth muscle actin, mouse
• Ovalbumin
• Collagen

Topics

• Actins (metabolism)
• Airway Remodeling
• Animals
• Bronchi (pathology)
• Bronchoalveolar Lavage Fluid (cytology)
• Cell Count
• Collagen (metabolism)
• Female
• Goblet Cells (metabolism, pathology)
• Hyperplasia
• Hypersensitivity (metabolism, pathology, physiopathology)
• Inflammation (complications, pathology)
• Lung (pathology)
• Mice, Inbred BALB C
• Mucus (metabolism)
• Ovalbumin
• Proliferating Cell Nuclear Antigen (metabolism)
• Receptors, Purinergic P2X4 (metabolism)