Role of the extracellular signal-regulated kinase 1/2 signaling pathway in the process of thrombin-promoting airway remodeling in ovalbumin-allergic rats. (February 2015)

• Record Type: Journal Article
• Authors: Bi, Meirong; Guo, Aili; Zhao, Hongyang; Sun, Xuewu; Chen, Qiang; Yu, Li; Shi, Wei; Wang, Yan; Shen, Guohong; Wang, Xueying; Zhao, Yingchun; Zhang, Nan; Xu, Mi; Qin, Mingming; Zhu, Weiwei
• Is Part Of: Immunopharmacology and immunotoxicology. Volume 37:Number 1(2015:Feb.)
• Page Start: 26
• Page End: 34
• Publication Date: 2015-02
• Subjects: Immunopharmacology -- Periodicals; Immunotoxicology -- Periodicals; Antibody-toxin conjugates -- Periodicals; Immunology -- Periodicals; 615.37
• DOI: 10.3109/08923973.2014.993083
• Languages: English
• ISSNs: 0892-3973

Abstract

<abstract> <title>Abstract</title> <p> <italic>Context</italic>: Although it is recognized that thrombin plays a key role in airway remodeling during chronic asthma. In a previous study, we have proved that thrombin promotes airway remodeling via PAR-1 in OVA-allergic rats, but little is known about intracellular signaling pathway involved in the event.</p> <p> <italic>Objective</italic>: In this study, we intend to explore the impact of pERK1/2 signaling pathway on the process of thrombin-induced airway remodeling in OVA-allergic rats.</p> <p> <italic>Materials and methods</italic>: A rat model of chronic asthma was set up by systemic sensitization and repeated challenge to OVA. The doses of thrombin, recombinant hirudin, PAR-1 inhibitor ER-112780-06, and pERK1/2 inhibitor PD98059 varied for different groups. The expression of pERK1/2 was analyzed by western blot and RT-PCR. Secretion of TGF-β1 and IL-6 was detected by ELISA.</p> <p> <italic>Results</italic>: The expression of pERK1/2 was higher in the airway of asthmatic rats than those of normal rats, and was significantly increased by thrombin treatment but decreased by thrombin-inhibitor treatment. Airway remodeling was enhanced by thrombin but weakened by pERK1/2 inhibitor. Expression of growth factors and IL-6 in asthmatic rats was significantly increased by thrombin treatment and decreased by thrombin-inhibitor treatment and pERK1/2 inhibitor treatment.</p> <p> <italic>Conclusion</italic>: These results suggest that ERK1/2 signaling pathway may play an important role in the process of thrombin-promoting airway remodeling in OVA-allergic rats, and pERK1/2 inhibitor effectively inhibits the process.</p> </abstract>