Influenza viruses can result in significant lung injury with significant morbidity and mortality. In this study, we evaluated the impact of cigarette smoke (CS) exposure on the pulmonary fibroblastic response after influenza infection. We used a murine model in which animals were exposed to CS or room air and subsequently infected with H1N1 influenza virus. Inflammatory and fibrotic responses were measured at different time points after influenza infection. Primary fibroblasts were isolated from the lungs of mice and their characteristics were evaluated. Exposure to CS significantly increased the amount of collagen in the lungs of mice infected with influenza virus compared with the nonsmoking group at 30 days after infection. Furthermore, the presence of fibroblast-specific protein-positive cells increased in the lungs of influenza-infected mice that were exposed to CS compared with the infection-alone group. The smoking group also showed delays in weight recovery and higher cell counts in BAL fluid after infection. Active transforming growth factor b1 levels in BAL fluid increased in both groups; however, CS-exposed mice had a later surge in active transforming growth factor b1 (Day 24). Ex vivo cultures of lung-derived fibroblasts from CS-exposed mice with influenza infection showed rapid proliferation, increased expression of a-smooth muscle actin-stained stress fibers, and higher expression of growth factors compared with fibroblasts from room air-exposed lungs after infection. These results suggest that CS exposure changes the fibroblastic potential, leading to increased fibrosis after influenza infection.
|Number of pages||12|
|Journal||American Journal of Respiratory Cell and Molecular Biology|
|Publication status||Published - 2018 Dec|
Bibliographical noteFunding Information:
Supported by National Heart, Lung, and Blood Institutes grants HL126094 and HL103770 (C.S.D.C.), and 1R01HL130283 (M.-J.K.).
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Pulmonary and Respiratory Medicine
- Clinical Biochemistry
- Cell Biology