2026-06-14T03:55:04Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/172692025-04-03T18:24:08Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19616

00925njm 22002777a 4500 dc Sivaraman, Kokilavani author Wrenger, Sabine author Liu, Bin author Schaudien, Dirk author Hesse, Christina author Gomez-Mariano, Gema Maria author Perez-Luz, Sara author Sewald, Katherina author DeLuca, David S author Wurm, Maria J author Pino, Paco author Welte, Tobias author Martinez-Delgado, Beatriz author Janciauskiene, Sabina author 2023-01-10 Rodent models of lipopolysaccharide (LPS)-induced pulmonary inflammation are used for anti-inflammatory drug testing. We aimed to characterize mice responses to aerosolized LPS alone or with intraperitoneal (i.p.) delivery of alpha1-antitrypsin (AAT). Balb/c mice were exposed to clean air or aerosolized LPS (0.21 mg/mL) for 10 min per day, for 3 d. One hour after each challenge, animals were treated i.p. with saline or with (4 mg/kg body weight) one of the AAT preparations: native (AAT), oxidized (oxAAT), recombinant (recAAT), or peptide of AAT (C-36). Experiments were terminated 6 h after the last dose of AATs. Transcriptome data of mice lungs exposed to clean air versus LPS revealed 656 differentially expressed genes and 155 significant gene ontology terms, including neutrophil migration and toll-like receptor signaling pathways. Concordantly, mice inhaling LPS showed higher bronchoalveolar lavage fluid neutrophil counts and levels of myeloperoxidase, inducible nitric oxide synthase, IL-1β, TNFα, KC, IL-6, and granulocyte-macrophage colony-stimulating factor (GM-CSF). Plasma inflammatory markers did not increase. After i.p. application of AATs, about 1% to 2% of proteins reached the lungs but, except for GM-CSF, none of the proteins significantly influenced inflammatory markers. All AATs and C-36 significantly inhibited LPS-induced GM-CSF release. Surprisingly, only oxAAT decreased the expression of several LPS-induced inflammatory genes, such as Cxcl3, Cd14, Il1b, Nfkb1, and Nfkb2, in lung tissues. According to lung transcriptome data, oxAAT mostly affected genes related to transcriptional regulation while native AAT or recAAT affected genes of inflammatory pathways. Hence, we present a feasible mice model of local lung inflammation induced via aerosolized LPS that can be useful for systemic drug testing. J Leukoc Biol. 2023 Jan 10;113(1):58-70. 10.1093/jleuko/qiac004 1938-3673 Journal of leukocyte biology 36822165 http://hdl.handle.net/20.500.12105/17269 Endotoxin inhalation Lung inflammation RNA-seq Cytokines Molecular forms Oxidation C-terminal peptide Mice inflammatory responses to inhaled aerosolized LPS: effects of various forms of human alpha1-antitrypsin