| First Author | Chen M | Year | 2015 |
| Journal | Am J Respir Cell Mol Biol | Volume | 53 |
| Issue | 3 | Pages | 346-54 |
| PubMed ID | 25569510 | Mgi Jnum | J:291304 |
| Mgi Id | MGI:6446441 | Doi | 10.1165/rcmb.2014-0231OC |
| Citation | Chen M, et al. (2015) Genetic Deletion of beta-Arrestin-2 and the Mitigation of Established Airway Hyperresponsiveness in a Murine Asthma Model. Am J Respir Cell Mol Biol 53(3):346-54 |
| abstractText | beta-Arrestin-2 (betaarr2) is a ubiquitously expressed cytosolic protein that terminates G protein-coupled receptor signaling and transduces G protein-independent signaling. We previously showed that mice lacking betaarr2 do not develop an asthma phenotype when sensitized to, and challenged with, allergens. The current study evaluates if an established asthma phenotype can be mitigated by deletion of betaarr2 using an inducible Cre recombinase. We sensitized and challenged mice to ovalbumin (OVA) and demonstrated that on Day (d) 24 the allergic asthma phenotype was apparent in uninduced betaarr2 and wild-type (WT) mice. In a second group of OVA-treated mice, tamoxifen was injected on d24 to d28 to activate Cre recombinase, and OVA aerosol challenge was continued through d44. The asthma phenotype was assessed using lung mechanics measurements, bronchoalveolar lavage cell analysis, and histological assessment of mucin and airway inflammation. Compared with their respective saline-treated controls, OVA-treated WT mice and mice expressing the inducible Cre recombinase displayed a significant asthma phenotype at d45. Whereas tamoxifen treatment had no significant effect on the asthma phenotype in WT mice, it inhibited betaarr2 expression and caused a significant reduction in airway hyper-responsiveness (AHR) in Cre-inducible mice. These findings suggest that betaarr2 is actively required for perpetuation of the AHR component of the allergic asthma phenotype. Our finding that betaarr2 participates in the perpetuation of AHR in an asthma model means that targeting betaarr2 may provide immediate and potentially long-term relief from daily asthma symptoms due to AHR irrespective of inflammation. |
