Crosstalk Between LXR and Caveolin-1 Signaling Supports Cholesterol Efflux and Anti-Inflammatory Pathways in Macrophages

Autor: Cristina M. Ramírez, Marta Torrecilla-Parra, Virginia Pardo-Marqués, Mario Fernández de-Frutos, Ana Pérez-García, Carlos Tabraue, Juan Vladimir de la Rosa, Patricia Martín-Rodriguez, Mercedes Díaz-Sarmiento, Uxue Nuñez, Marta C. Orizaola, Paqui G. Través, Marta Camps, Lisardo Boscá, Antonio Castrillo
Přispěvatelé: Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Ministerio de Economía, Industria y Competitividad (España), Centro de Investigación Biomédica en Red Enfermedades Cardiovaculares (España), Comunidad de Madrid, European Commission
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
Transcription
Genetic
Macrophage
Endocrinology
Diabetes and Metabolism
Caveolin 1
Detergents
Green Fluorescent Proteins
Anti-Inflammatory Agents
Inflammation
Diseases of the endocrine glands. Clinical endocrinology
Mice
03 medical and health sciences
Endocrinology
0302 clinical medicine
Immune system
Caveolin-1
Caveolae
medicine
Animals
Humans
Cholesterol efflux
Liver X receptor
Transcription factor
Original Research
Liver X Receptors
Apolipoprotein A-I
Chemistry
Macrophages
Cell Membrane
Atherosclerosis
RC648-665
Cell biology
Mice
Inbred C57BL
Crosstalk (biology)
Cholesterol
RAW 264.7 Cells
030104 developmental biology
cardiovascular system
lipids (amino acids
peptides
and proteins)
LXR
Gene expression
medicine.symptom
030217 neurology & neurosurgery
ATP Binding Cassette Transporter 1
Signal Transduction
Zdroj: Digital.CSIC. Repositorio Institucional del CSIC
instname
Frontiers in Endocrinology, Vol 12 (2021)
Frontiers in Endocrinology
ISSN: 1664-2392
DOI: 10.3389/fendo.2021.635923
Popis: © 2021 Ramírez, Torrecilla-Parra, Pardo-Marqués, de-Frutos, Pérez-García, Tabraue, de la Rosa, Martín-Rodriguez, Díaz-Sarmiento, Nuñez, Orizaola, Través, Camps, Boscá and Castrillo.
Macrophages are immune cells that play crucial roles in host defense against pathogens by triggering their exceptional phagocytic and inflammatory functions. Macrophages that reside in healthy tissues also accomplish important tasks to preserve organ homeostasis, including lipid uptake/efflux or apoptotic-cell clearance. Both homeostatic and inflammatory functions of macrophages require the precise stability of lipid-rich microdomains located at the cell membrane for the initiation of downstream signaling cascades. Caveolin-1 (Cav-1) is the main protein responsible for the biogenesis of caveolae and plays an important role in vascular inflammation and atherosclerosis. The Liver X receptors (LXRs) are key transcription factors for cholesterol efflux and inflammatory gene responses in macrophages. Although the role of Cav-1 in cellular cholesterol homeostasis and vascular inflammation has been reported, the connection between LXR transcriptional activity and Cav-1 expression and function in macrophages has not been investigated. Here, using gain and loss of function approaches, we demonstrate that LXR-dependent transcriptional pathways modulate Cav-1 expression and compartmentation within the membrane during macrophage activation. As a result, Cav-1 participates in LXR-dependent cholesterol efflux and the control of inflammatory responses. Together, our data show modulation of the LXR-Cav-1 axis could be exploited to control exacerbated inflammation and cholesterol overload in the macrophage during the pathogenesis of lipid and immune disorders, such as atherosclerosis.
We thank MINECO FPI predoctoral fellowship granted to MCO (BES-2015-075339). Experimental work was supported by grants from Ministerio de Ciencia, Investigación y Universidades, y Fondo Europeo de Desarrollo Regional (FEDER) Grant REF: PID2019-104284RB-I00/AEI/10.13039/501100011033 (to AC) and support from Networks of Excellence from MINECO (Nuclear Receptors in Cancer, Metabolism and Inflammation [NuRCaMeIn] SAF2017-90604-REDT to AC. Ministerio de Economía, Industria y Competitividad, Ministerio de Ciencia, Investigación y Universidades, and Agencia Estatal de Investigación (SAF2017-82436-R, RTC2017-6283-1), Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares (CB16/11/00222), Consorcio de Investigación en Red de la Comunidad de Madrid, S2017/BMD-3686 and Fondo Europeo de Desarrollo Regional (to LB). Ministerio de Ciencia, Investigación y Universidades, and Agencia Estatal de Investigación Proyectos de I+D+i Retos Investigación 2018 (RTI2018-095061-B-I00); TALENTO Grant from Madrid Government, Spain (2017-T1/BMD-5333); Consejería de Ciencia, Universidades e Innovación Comunidad de Madrid, Spain (PEJD-2018-POST/BMD-8900 and PEDJ-2018-AI/BDM-9724) to CMR.
Databáze: OpenAIRE
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