| First Author | Zhou Y | Year | 2013 |
| Journal | J Immunol | Volume | 191 |
| Issue | 5 | Pages | 2637-46 |
| PubMed ID | 23913960 | Mgi Jnum | J:205811 |
| Mgi Id | MGI:5546478 | Doi | 10.4049/jimmunol.1300082 |
| Citation | Zhou Y, et al. (2013) Role of ribonuclease L in viral pathogen-associated molecular pattern/influenza virus and cigarette smoke-induced inflammation and remodeling. J Immunol 191(5):2637-46 |
| abstractText | Interactions between cigarette smoke (CS) exposure and viral infection play an important role(s) in the pathogenesis of chronic obstructive pulmonary disease and a variety of other disorders. A variety of lines of evidence suggest that this interaction induces exaggerated inflammatory, cytokine, and tissue remodeling responses. We hypothesized that the 2'-5' oligoadenylate synthetase (OAS)/RNase L system, an innate immune antiviral pathway, plays an important role in the pathogenesis of these exaggerated responses. To test this hypothesis, we characterize the activation of 2'-5' OAS in lungs from mice exposed to CS and viral pathogen-associated molecular patterns (PAMPs)/live virus, alone and in combination. We also evaluated the inflammatory and remodeling responses induced by CS and virus/viral PAMPs in lungs from RNase L null and wild-type mice. These studies demonstrate that CS and viral PAMPs/live virus interact in a synergistic manner to stimulate the production of select OAS moieties. They also demonstrate that RNase L plays a critical role in the pathogenesis of the exaggerated inflammatory, fibrotic, emphysematous, apoptotic, TGF-beta1, and type I IFN responses induced by CS plus virus/viral PAMP in combination. These studies demonstrate that CS is an important regulator of antiviral innate immunity, highlight novel roles of RNase L in CS plus virus induced inflammation, tissue remodeling, apoptosis, and cytokine elaboration and highlight pathways that may be operative in chronic obstructive pulmonary disease and mechanistically related disorders. |
