Impact of cigarette smoke exposure on the lung fibroblastic response after influenza pneumonia

Sei Won Lee, Lokesh Sharma, Young Ae Kang, Sang Hun Kim, Sreelakshmi Chandrasekharan, Ashley Losier, Virginia Brady, Santos Bermejo, Nathaniel Andrews, Chang Min Yoon, Wei Liu, Jung Yeon Lee, Min Jong Kang, Charles S.Dela Cruz

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)770-781
Number of pages12
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Issue number6
Publication statusPublished - 2018 Dec

Bibliographical note

Funding Information:
Supported by National Heart, Lung, and Blood Institutes grants HL126094 and HL103770 (C.S.D.C.), and 1R01HL130283 (M.-J.K.).

Publisher Copyright:
Copyright © 2018 by the American Thoracic Society.

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology


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