Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/17269
Título
Mice inflammatory responses to inhaled aerosolized LPS: effects of various forms of human alpha1-antitrypsin
Autor(es)
Sivaraman, Kokilavani | Wrenger, Sabine | Liu, Bin | Schaudien, Dirk | Hesse, Christina | Gomez-Mariano, Gema Maria ISCIII | Perez-Luz, Sara ISCIII | Sewald, Katherina | DeLuca, David | Wurm, Maria J | Pino, Paco | Welte, Tobias | Martinez-Delgado, Beatriz ISCIII | Janciauskiene, Sabina
Fecha de publicación
2023-01-10
Cita
J Leukoc Biol. 2023 Jan 10;113(1):58-70.
Idioma
Inglés
Tipo de documento
research article
Resumen
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.
Palabras clave
Endotoxin inhalation | Lung inflammation | RNA-seq | Cytokines | Molecular forms | Oxidation | C-terminal peptide
MESH
Granulocyte-Macrophage Colony-Stimulating Factor | Pneumonia | alpha 1-Antitrypsin | Animals | Humans | Mice | Bronchoalveolar Lavage Fluid | Lipopolysaccharides | Lung
Versión en línea
DOI
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