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

Sei Won Lee, Lokesh Sharma, youngae 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 journalArticle

1 Citation (Scopus)

Abstract

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
Volume59
Issue number6
DOIs
Publication statusPublished - 2018 Dec 1

Fingerprint

Smoke
Tobacco Products
Human Influenza
Pneumonia
Lung
Fibroblasts
Infection
Viruses
Orthomyxoviridae
Dimercaprol
Transforming Growth Factors
Air
Fluids
H1N1 Subtype Influenza A Virus
Stress Fibers
Cell culture
Lung Injury
Muscle
Actins
Intercellular Signaling Peptides and Proteins

All Science Journal Classification (ASJC) codes

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

Cite this

Lee, Sei Won ; Sharma, Lokesh ; kang, youngae ; Kim, Sang Hun ; Chandrasekharan, Sreelakshmi ; Losier, Ashley ; Brady, Virginia ; Bermejo, Santos ; Andrews, Nathaniel ; Yoon, Chang Min ; Liu, Wei ; Lee, Jung Yeon ; Kang, Min Jong ; Cruz, Charles S.Dela. / Impact of cigarette smoke exposure on the lung fibroblastic response after influenza pneumonia. In: American Journal of Respiratory Cell and Molecular Biology. 2018 ; Vol. 59, No. 6. pp. 770-781.
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abstract = "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.",
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Lee, SW, Sharma, L, kang, Y, Kim, SH, Chandrasekharan, S, Losier, A, Brady, V, Bermejo, S, Andrews, N, Yoon, CM, Liu, W, Lee, JY, Kang, MJ & Cruz, CSD 2018, 'Impact of cigarette smoke exposure on the lung fibroblastic response after influenza pneumonia', American Journal of Respiratory Cell and Molecular Biology, vol. 59, no. 6, pp. 770-781. https://doi.org/10.1165/rcmb.2018-0004OC

Impact of cigarette smoke exposure on the lung fibroblastic response after influenza pneumonia. / Lee, Sei Won; Sharma, Lokesh; kang, youngae; Kim, Sang Hun; Chandrasekharan, Sreelakshmi; Losier, Ashley; Brady, Virginia; Bermejo, Santos; Andrews, Nathaniel; Yoon, Chang Min; Liu, Wei; Lee, Jung Yeon; Kang, Min Jong; Cruz, Charles S.Dela.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 59, No. 6, 01.12.2018, p. 770-781.

Research output: Contribution to journalArticle

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T1 - Impact of cigarette smoke exposure on the lung fibroblastic response after influenza pneumonia

AU - Lee, Sei Won

AU - Sharma, Lokesh

AU - kang, youngae

AU - Kim, Sang Hun

AU - Chandrasekharan, Sreelakshmi

AU - Losier, Ashley

AU - Brady, Virginia

AU - Bermejo, Santos

AU - Andrews, Nathaniel

AU - Yoon, Chang Min

AU - Liu, Wei

AU - Lee, Jung Yeon

AU - Kang, Min Jong

AU - Cruz, Charles S.Dela

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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.

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