Scavenger receptor BI attenuates oxidized phospholipid-induced pulmonary inflammation

Dunigan-Russell, Katelyn; Yaeger, Michael J.; Hodge, Myles; Kilburg-Basnyat, Brita; Reece, Sky W.; Birukova, Anastasiya; Guttenberg, Marissa A; Novak, Caymen; Chung, Sangwoon; Ehrmann, Brandie M.; Wallace, E. Diane; Tokarz, Debra A; Majumder, Nairrita; Li, Xia; Christman, John W.; Shannahan, Jonathan H.; Ballinger, Megan N.; Hussain, Salik; Shaikh, Saame Raza; Tighe, Robert; Gowdy, Kymberly M.

doi:10.1016/j.taap.2023.116381

Cited by 8 publications

(5 citation statements)

References 78 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, there was a significant decrease in Scarb1 expression in male BMDM polarized to the M1 phenotype (Figure 5C), suggesting macrophage interaction with HDL may be altered during phenotype shifts. Therefore, we employed SR‐BI KO BMDM, 47 as a useful model of disrupted homeostatic cholesterol movement, both uptake and efflux, to assess the impacts on the phenotype polarization process.…”

Section: Resultsmentioning

confidence: 99%

“…Male SR-BI deficient mice (B6;129S2-Scarb1 tm1Kri /J, SR-BI −/− ) 47,48 were housed at The Ohio State University where tibia and femur bones from the hind legs were collected and shipped in complete media to the University of Montana for bone marrow isolation and culture (described elsewhere in Methods). All experiments were performed in accordance with the Animal Welfare Act and the U.S. Public Health Service Policy on Humane Care and Use of Laboratory Animals after review by The Ohio State University.…”

Section: Micementioning

confidence: 99%

See 1 more Smart Citation

Estrogen contributes to sex differences in M2a macrophages during multi‐walled carbon nanotube‐induced respiratory inflammation

Ray,

Postma,

Kendall

et al. 2023

The FASEB Journal

Self Cite

View full text Add to dashboard Cite

Lung diseases characterized by type 2 inflammation are reported to occur with a female bias in prevalence/severity in both humans and mice. This includes previous work examining multi‐walled carbon nanotube (MWCNT)‐induced eosinophilic inflammation, in which a more exaggerated M2a phenotype was observed in female alveolar macrophages (AMs) compared to males. The mechanisms responsible for this sex difference in AM phenotype are still unclear, but estrogen receptor (ER) signaling is a likely contributor. Accordingly, male AMs downregulated ERα expression after MWCNT exposure while female AMs did not. Thus, ER antagonist Fulvestrant was administered prior to MWCNT instillation. In females, Fulvestrant significantly attenuated MWCNT‐induced M2a gene expression and eosinophilia without affecting IL‐33. In males, Fulvestrant did not affect eosinophil recruitment but reduced IL‐33 and M2a genes compared to controls. Regulation of cholesterol efflux and oxysterol synthesis is a potential mechanism through which estrogen promotes the M2a phenotype. Levels of oxysterols 25‐OHC and 7α,25‐OHC were higher in the airways of MWCNT‐exposed males compared to MWCNT‐females, which corresponds with the lower IL‐1β production and greater macrophage recruitment previously observed in males. Sex‐based changes in cholesterol efflux transporters Abca1 and Abcg1 were also observed after MWCNT exposure with or without Fulvestrant. In vitro culture with estrogen decreased cellular cholesterol and increased the M2a response in female AMs, but did not affect cholesterol content in male AMs and reduced M2a polarization. These results reveal the modulation of (oxy)sterols as a potential mechanism through which estrogen signaling may regulate AM phenotype resulting in sex differences in downstream respiratory inflammation.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Micementioning

confidence: 99%

Estrogen contributes to sex differences in M2a macrophages during multi‐walled carbon nanotube‐induced respiratory inflammation

Ray,

Postma,

Kendall

et al. 2023

The FASEB Journal

Self Cite

View full text Add to dashboard Cite

show abstract

“…37 In this regard, ONE modification of HDL could impact its interaction with SR-BI, which also mediates inflammatory signaling in response to lipopolysaccharide. 94,153,154 Interestingly, MDA-HDL enhances lipopolysaccharide-induced expression of IL-1β and IL-6, but it is not as proinflammatory as IsoLG-HDL. 34,36 The proinflammatory nature of IsoLG-HDL and MDA-HDL suggests interaction with receptors that mediate inflammatory signaling pathways such as CD36 and LOX-1.…”

Section: Oxidative Modification Of Hdl Causes Hdl Dysfunctionmentioning

confidence: 96%

“…151,152 Furthermore, HDL interacts with SR-BI to activate Akt and suppress p38, Jnk (c-Jun N-terminal kinase), and NF-κB activation and TLR expression. 94,153,154 The suppression of NF-κB activation by HDL/apoAI reduces expression of the NLRP3 inflammasome components, thereby reducing TLR priming of inflammasome activation and secretion of IL-1β and IL-18 in response to other signals such as excess FC (Figure 3). 155,156 One of the most important processes to reduce uncontrolled inflammation, necrotic death, and formation of the vulnerable plaque is the efficient efferocytosis of apoptotic cells, 9 and evidence is accumulating that HDL facilitates macrophage efferocytosis.…”

Section: Hdl Anti-inflammatory Functionmentioning

confidence: 99%

HDL Function and Atherosclerosis: Reactive Dicarbonyls as Promising Targets of Therapy

Linton

Yancey

Huan

et al. 2023

Circulation Research

View full text Add to dashboard Cite

Epidemiologic studies detected an inverse relationship between HDL (high-density lipoprotein) cholesterol (HDL-C) levels and atherosclerotic cardiovascular disease (ASCVD), identifying HDL-C as a major risk factor for ASCVD and suggesting atheroprotective functions of HDL. However, the role of HDL-C as a mediator of risk for ASCVD has been called into question by the failure of HDL-C–raising drugs to reduce cardiovascular events in clinical trials. Progress in understanding the heterogeneous nature of HDL particles in terms of their protein, lipid, and small RNA composition has contributed to the realization that HDL-C levels do not necessarily reflect HDL function. The most examined atheroprotective function of HDL is reverse cholesterol transport, whereby HDL removes cholesterol from plaque macrophage foam cells and delivers it to the liver for processing and excretion into bile. Indeed, in several studies, HDL has shown inverse associations between HDL cholesterol efflux capacity and ASCVD in humans. Inflammation plays a key role in the pathogenesis of atherosclerosis and vulnerable plaque formation, and a fundamental function of HDL is suppression of inflammatory signaling in macrophages and other cells. Oxidation is also a critical process to ASCVD in promoting atherogenic oxidative modifications of LDL (low-density lipoprotein) and cellular inflammation. HDL and its proteins including apoAI (apolipoprotein AI) and PON1 (paraoxonase 1) prevent cellular oxidative stress and LDL modifications. Importantly, HDL in humans with ASCVD is oxidatively modified rendering HDL dysfunctional and proinflammatory. Modification of HDL with reactive carbonyl species, such as malondialdehyde and isolevuglandins, dramatically impairs the antiatherogenic functions of HDL. Importantly, treatment of murine models of atherosclerosis with scavengers of reactive dicarbonyls improves HDL function and reduces systemic inflammation, atherosclerosis development, and features of plaque instability. Here, we discuss the HDL antiatherogenic functions in relation to oxidative modifications and the potential of reactive dicarbonyl scavengers as a therapeutic approach for ASCVD.

show abstract

“…Largely expressed in immune and non-immune cells, CD36 plays important immunomodulatory roles in health and disease ( Silverstein and Febbraio, 2009 ). First identified as a long chain fatty acid transporter, CD36 has been later shown to mediate inflammatory signaling in response to damage-associated molecular pattern signals (DAMPs), such as oxidized phospholipids (oxPLs) ( Miller et al, 2011 ; Chen et al, 2022 ; Dunigan-Russell et al, 2023 ). The binding domain for oxPLs has been identified in the CD36 protein ( Ashraf et al, 2009 ).…”

Section: Introductionmentioning

confidence: 99%

Pharmacological targeting of the hyper-inflammatory response to SARS-CoV-2-infected K18-hACE2 mice using a cluster of differentiation 36 receptor modulator

Gauvin,

Huynh,

Dubuc

et al. 2024

Front. Pharmacol.

View full text Add to dashboard Cite

The scientific and medical community faced an unprecedented global health hazard that led to nearly 7 million deaths attributable to the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In spite of the development of efficient vaccines against SARS-CoV-2, many people remain at risk of developing severe symptoms as the virus continues to spread without beneficial patient therapy. The hyper-inflammatory response to SARS-CoV-2 infection progressing to acute respiratory distress syndrome remains an unmet medical need for improving patient care. The viral infection stimulates alveolar macrophages to adopt an inflammatory phenotype regulated, at least in part, by the cluster of differentiation 36 receptor (CD36) to produce unrestrained inflammatory cytokine secretions. We suggest herein that the modulation of the macrophage response using the synthetic CD36 ligand hexarelin offers potential as therapy for halting respiratory failure in SARS-CoV-2-infected patients.

show abstract

Scavenger receptor BI attenuates oxidized phospholipid-induced pulmonary inflammation

Cited by 8 publications

References 78 publications

Estrogen contributes to sex differences in M2a macrophages during multi‐walled carbon nanotube‐induced respiratory inflammation

Estrogen contributes to sex differences in M2a macrophages during multi‐walled carbon nanotube‐induced respiratory inflammation

HDL Function and Atherosclerosis: Reactive Dicarbonyls as Promising Targets of Therapy

Pharmacological targeting of the hyper-inflammatory response to SARS-CoV-2-infected K18-hACE2 mice using a cluster of differentiation 36 receptor modulator

Contact Info

Product

Resources

About