PT  - JOURNAL ARTICLE
AU  - Stiliyanov Atanasov, K
AU  - Truyols Vives, J
AU  - Escarrer, G
AU  - Gómez, C
AU  - De Francisco, T
AU  - Martín Medina, A
AU  - Río, C
AU  - Sala-Llinàs, E
AU  - Mercader-Barceló, J
TI  - Profibrotic effects analysis of bleomycin administration in Swiss CD-1 nude mice
AID  - 10.1183/13993003.congress-2022.4119
DP  - 2022 Sep 04
TA  - European Respiratory Journal
PG  - 4119
VI  - 60
IP  - suppl 66
4099  - https://publications.ersnet.org//content/60/suppl_66/4119.short
4100  - https://publications.ersnet.org//content/60/suppl_66/4119.full
SO  - Eur Respir J2022 Sep 04; 60
AB  - The benefits of cell therapy observed in inbred mice treated with bleomycin (BLM) are difficultly translated into idiopathic pulmonary fibrosis (IPF) patients due to model limitations. The use of outbred strains might better model IPF pathogenesis and therapy responses. Furthermore, the use of nude mice is a viable model for human cell transplantation. The aim of the study was to characterize the BLM response of Swiss CD-1 nude mice. First, male nu/+ and nu/nu mice were used to analyse the effects of i.t. administration of 2 U/kg BLM at days 4, 10, 14 and 28. Second, the effects of 2, 6 and 12 U/kg were characterized in female nu/+ and nu/nu mice at day 14. PF was evaluated by Ashcroft score. Collagen lung content was analysed by Sirius red. Bronchoalveolar lavage fluid (BALF) cell count was manually performed. Gene expression was analysed by RT-PCR and western blot. Male nu/+ and nu/nu mice developed mild yet significant PF. Col1a1 levels were induced in both genotypes, while Fn1 and Acta2 levels were induced only in nu/+ mice. Il6 and Tnfα induction by BLM was blunted in nu/nu mice. BALF total nucleated cell and macrophage counts were increased in nu/+ mice and were blunted in nu/nu mice. Female nu/+ and nu/nu mice did not develop significant PF according to histological analysis. Only Fn1 was upregulated in response to 6 U/kg BLM in nu/+ females. BLM-treated nu/nu female mice showed no changes in molecular parameters. Swiss mice are less sensitive to BLM compared other strains. The lower induction of inflammatory markers in nu/nu mice might mitigate the profibrotic effect of BLM. These results should be taken into account before investigating the effects of therapeutic agents.FootnotesCite this article as Eur Respir J 2022; 60: Suppl. 66, 4119.This article was presented at the 2022 ERS International Congress, in session “-”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).