EXPERIMENTAL MOUSE MODEL OF PULMONARY FIBROSIS INDUCED BY NEBULIZED LPS ADMINISTRATION
- Authors: Namakanova O.A.1,2, Gubernatorova E.O.1,2, Chicherina N.R.3, Zvartsev R.V.1,2, Drutskaya M.S.1,2,3
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Affiliations:
- Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russian Federation
- Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russian Federation
- Sirius University of Science and Technology, Krasnodar Region, Russian Federation
- Section: Joint Immunology Forum 2024
- URL: https://rusimmun.ru/jour/article/view/16876
- DOI: https://doi.org/10.46235/1028-7221-16876-EMM
- ID: 16876
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Abstract
Abstract
Lipopolysaccharide (LPS)-induced lung injury is the most commonly used mouse model of acute lung inflammation that simulate the development of respiratory distress syndrome in human. The effects of acute LPS-induced airway inflammation are well studied and associated with the neutrophil accumulation in bronchoalveolar lavage fluid (BALF), local and systemic production of proinflammatory cytokines and narrowing of the airways. Recent studies demonstrated the presence of pulmonary fibrosis characterized by increased fibroblast proliferation and excess extracellular matrix deposition in late phase of acute lung inflammation caused by LPS exposure. This work describes an experimental model of acute lung injury induced by a single aerosol injection of LPS as a reproducible in vivo model of pulmonary fibrosis. To induce lung injury C57BL/6 mice were placed in a chamber and exposed to an aerosol containing 10 mg of LPS using an Aeroneb Lab Nebulizer delivery system.
We found that 5 weeks after a single nebulized LPS administration, mice have increased production of IL-6 in BALF. Although the frequency of neutrophils was not altered, there was a decrease in the percentage of alveolar macrophages at 5 weeks after LPS exposure, indicating continued lung inflammation. Several weeks after aerosolized LPS challenge IL-10 production in BALF was increased, as well as expression of Tgfb1, Col1a1, Il13 and Acta2, and collagen deposition in lung tissue compared to mice with acute lung inflammation.
Thus, the single nebulized LPS administration represents a relevant, reproducible and physiologic model in mice allowing to investigate the mechanisms of pulmonary fibrosis development and help in the search for new therapeutic agents and approaches.
About the authors
Olga A. Namakanova
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russian Federation;Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russian Federation
Author for correspondence.
Email: olga.namakanova@gmail.com
ORCID iD: 0000-0001-6423-5843
Junior Research Associate, Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russian Federation
Russian Federation, 32, Vavilov st., Moscow, Russia, 119334Ekaterina O. Gubernatorova
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russian Federation;Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russian Federation
Email: ekaterina.gubernatorova412@gmail.com
Senior Research Associate, Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russian Federation
Russian Federation, Ул. Вавилова, 32, Москва, Россия, 119334.Nelya R. Chicherina
Sirius University of Science and Technology, Krasnodar Region, Russian Federation
Email: nelyayakhina@mail.ru
Master student, Division of Immunobiology and Biomedicine, Sirius University of Science and Technology, Krasnodar Region, Russian Federation
Russian FederationRuslan V. Zvartsev
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russian Federation;Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russian Federation
Email: r.zvartsev@gmail.com
Junior Research Associate, Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russian Federation
Russian FederationMarina S. Drutskaya
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russian Federation;Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russian Federation;
Sirius University of Science and Technology, Krasnodar Region, Russian Federation
Email: marinadru@gmail.com
PhD, MD (Biology), Leading Research Associate, Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow; Assistant Professor, Sirius University of Science and Technology, Krasnodar Region, Russian Federation
Russian Federation