Version 1
: Received: 29 July 2024 / Approved: 29 July 2024 / Online: 30 July 2024 (07:39:13 CEST)
How to cite:
Richards, C. D.; Ayaub, E.; Botelho, F.; Dvorkin-Gheva, A.; Vierhout, M.; Naiel, S.; Abed, S.; Kolb, M.; Ask, K. Overexpression of Il-6 in Bleomycin-Treated Balb/C Mice Provides a New Model of Lung Fibrosis: Transcriptomic Comparison to Human Ipf. Preprints2024, 2024072361. https://doi.org/10.20944/preprints202407.2361.v1
Richards, C. D.; Ayaub, E.; Botelho, F.; Dvorkin-Gheva, A.; Vierhout, M.; Naiel, S.; Abed, S.; Kolb, M.; Ask, K. Overexpression of Il-6 in Bleomycin-Treated Balb/C Mice Provides a New Model of Lung Fibrosis: Transcriptomic Comparison to Human Ipf. Preprints 2024, 2024072361. https://doi.org/10.20944/preprints202407.2361.v1
Richards, C. D.; Ayaub, E.; Botelho, F.; Dvorkin-Gheva, A.; Vierhout, M.; Naiel, S.; Abed, S.; Kolb, M.; Ask, K. Overexpression of Il-6 in Bleomycin-Treated Balb/C Mice Provides a New Model of Lung Fibrosis: Transcriptomic Comparison to Human Ipf. Preprints2024, 2024072361. https://doi.org/10.20944/preprints202407.2361.v1
APA Style
Richards, C. D., Ayaub, E., Botelho, F., Dvorkin-Gheva, A., Vierhout, M., Naiel, S., Abed, S., Kolb, M., & Ask, K. (2024). Overexpression of Il-6 in Bleomycin-Treated Balb/C Mice Provides a New Model of Lung Fibrosis: Transcriptomic Comparison to Human Ipf. Preprints. https://doi.org/10.20944/preprints202407.2361.v1
Chicago/Turabian Style
Richards, C. D., Martin Kolb and Kjetil Ask. 2024 "Overexpression of Il-6 in Bleomycin-Treated Balb/C Mice Provides a New Model of Lung Fibrosis: Transcriptomic Comparison to Human Ipf" Preprints. https://doi.org/10.20944/preprints202407.2361.v1
Abstract
Idiopathic pulmonary fibrosis (IPF) is a difficult to treat condition to treat with a high mortality rate. While preclinical models such as Bleomycin (Bleo)-induced fibrosis recapitulate some aspects of IPF, new models that more closely mimic the disease are warranted. We have developed and characterized a novel model in BALB/c mice using a transient overexpression of IL-6 combined with Bleo. This model’s transcriptomic signature was compared to published human IPF datasets. BALB/c females were treated with AdIL-6 in combination with Bleo (AdIL-6+Bleo) or control comparators, and underwent assessments of histopathology (ECM, α-SMA accumulation), collagen content and lung physiology (Elastance, EST). Flow cytometry was used to characterize T cell and Macrophage subsets, and T cell depletion studies (anti-CD4/CD8) were completed to assess T cells role in fibrosis. Bulk RNA sequencing generated gene signatures were compared to that of other rodent fibrosis models and published human datasets of IPF datasets. The AdIL-6+Bleo treatment resulted in robust fibrosis measures (day21), sustained fibrosis until at least day 50, a unique cytokine profile at day 7, and increased activated CD4+Tcells, CD8+Tcells, and CD16+MHChi/Clec7a/iNOS-/Arg1-/CD206- macrophages. T cell depletion markedly decreased fi-brotic responses and this population of macrophages. The Day 21 AdIL-6+Bleo transcriptome shared more genes with each of two human IPF datasets than Bleo alone in C57Bl/6 mice or other rodent models. We conclude that AdIL-6+Bleo in BALB/c mice offers a superior preclinical model for studying IPF mechanisms and potential therapeutic intervention.
Medicine and Pharmacology, Pulmonary and Respiratory Medicine
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
