Please use this identifier to cite or link to this item: http://hdl.handle.net/10553/132057
Title: Endogenous LXR signaling controls pulmonary surfactant homeostasis and prevents lung inflammation
Authors: Hernández Hernández, Irene 
De La Rosa Medina, Juan Vladimir 
Martín Rodríguez, Patricia 
Diaz Sarmiento,Maria Mercedes 
Recio Cruz, Carlota Pilar 
Guerra Hernández, Carlos Borja 
Fernández Pérez, Leandro Francisco 
León, Theresa E.
Torres, Rosa
Font-Díaz, Joan
Roig, Angela
de Mora, Fernando
Boscá, Lisardo
Díaz González, Mario Lorenzo 
Valledor Annabel F.
Castrillo Viguera, Antonio Jesús 
Tabraue Tarbay, Carlos 
UNESCO Clasification: 32 Ciencias médicas
Keywords: LXR
Alveolar macrophage
Type 2 pneumocyte
Surfactant
Inflammation, et al
Issue Date: 2024
Project: PID2019-104284RBI00
PID2022-137696OB-I00
PID2020-119875RB-I00
SAF2017-89510-R
SAF2017-90604-REDT
PI18/01702
PROID2017010050
PRE2018-085579
BES200901219
Journal: Cellular and Molecular Life Sciences 
Abstract: Lung type 2 pneumocytes (T2Ps) and alveolar macrophages (AMs) play crucial roles in the synthesis, recycling and catabolism of surfactant material, a lipid/protein fluid essential for respiratory function. The liver X receptors (LXR), LXRα and LXRβ, are transcription factors important for lipid metabolism and inflammation. While LXR activation exerts anti-inflammatory actions in lung injury caused by lipopolysaccharide (LPS) and other inflammatory stimuli, the full extent of the endogenous LXR transcriptional activity in pulmonary homeostasis is incompletely understood. Here, using mice lacking LXRα and LXRβ as experimental models, we describe how the loss of LXRs causes pulmonary lipidosis, pulmonary congestion, fibrosis and chronic inflammation due to defective de novo synthesis and recycling of surfactant material by T2Ps and defective phagocytosis and degradation of excess surfactant by AMs. LXR-deficient T2Ps display aberrant lamellar bodies and decreased expression of genes encoding for surfactant proteins and enzymes involved in cholesterol, fatty acids, and phospholipid metabolism. Moreover, LXR-deficient lungs accumulate foamy AMs with aberrant expression of cholesterol and phospholipid metabolism genes. Using a house dust mite aeroallergen-induced mouse model of asthma, we show that LXR-deficient mice exhibit a more pronounced airway reactivity to a methacholine challenge and greater pulmonary infiltration, indicating an altered physiology of LXR-deficient lungs. Moreover, pretreatment with LXR agonists ameliorated the airway reactivity in WT mice sensitized to house dust mite extracts, confirming that LXR plays an important role in lung physiology and suggesting that agonist pharmacology could be used to treat inflammatory lung diseases.
URI: http://hdl.handle.net/10553/132057
ISSN: 1420-682X
DOI: 10.1007/s00018-024-05310-3
Source: Cellular and Molecular Life Sciences [ISSN 1420-682X], v. 81 (287), (Julio 2024).
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