| First Author | Gahring LC | Year | 2018 |
| Journal | Am J Physiol Lung Cell Mol Physiol | Volume | 315 |
| Issue | 4 | Pages | L553-L562 |
| PubMed ID | 29975102 | Mgi Jnum | J:266172 |
| Mgi Id | MGI:6201854 | Doi | 10.1152/ajplung.00230.2018 |
| Citation | Gahring LC, et al. (2018) Lung eosinophilia induced by house dust mites or ovalbumin is modulated by nicotinic receptor alpha7 and inhibited by cigarette smoke. Am J Physiol Lung Cell Mol Physiol 315(4):L553-L562 |
| abstractText | Eosinophilia (EOS) is an important component of airway inflammation and hyperresponsiveness in allergic reactions including those leading to asthma. Although cigarette smoking (CS) is a significant contributor to long-term adverse outcomes in these lung disorders, there are also the curious reports of its ability to produce acute suppression of inflammatory responses including EOS through poorly understood mechanisms. One possibility is that proinflammatory processes are suppressed by nicotine in CS acting through nicotinic receptor alpha7 (alpha7). Here we addressed the role of alpha7 in modulating EOS with two mouse models of an allergic response: house dust mites (HDM; Dermatophagoides sp.) and ovalbumin (OVA). The influence of alpha7 on EOS was experimentally resolved in wild-type mice or in mice in which a point mutation of the alpha7 receptor (alpha7(E260A:G)) selectively restricts normal signaling of cellular responses. RNA analysis of alveolar macrophages and the distal lung epithelium indicates that normal alpha7 function robustly impacts gene expression in the epithelium to HDM and OVA but to different degrees. Notable was allergen-specific alpha7 modulation of Ccl11 and Ccl24 (eotaxins) expression, which was enhanced in HDM but suppressed in OVA EOS. CS suppressed EOS induced by both OVA and HDM, as well as the inflammatory genes involved, regardless of alpha7 genotype. These results suggest that EOS in response to HDM or OVA is through signaling pathways that are modulated in a cell-specific manner by alpha7 and are distinct from CS suppression. |
