Macrophage SR-BI regulates LPS-induced pro-inflammatory signaling in mice and isolated macrophages

Cai, Lei; Wang, Zhen; Meyer, Jason M.; Ji, Ailing; Westhuyzen, Deneys R. van der

doi:10.1194/jlr.m023234

Cited by 59 publications

(36 citation statements)

References 43 publications

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Section: Discussionmentioning

confidence: 96%

“…Thus, SR-BI could exert a beneficial role in macrophages by partially inhibiting the inflammatory response to LPS (9,16). In vivo, an enhanced proinflammatory response to LPS in irradiated wild-type mice reconstituted with SR-BI mice receiving wild-type BM cells would indeed support the existence of an anti-inflammatory activity of SR-BI in BM-derived cells (16). However, our data in the hypomSR-BI; LysM-Cre mouse model revealed a moderately reduced inflammatory response to LPS, suggesting an overall LPS-induced proinflammatory action of SR-BI expressed in monocytes/macrophages and/or granulocytes in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…In this context, SR-BI has been shown to exert an anti-inflammatory action in LPS-stimulated macrophages, potentially dampening TLR4-mediated NF-kB activation (9,16), but also interfering with the JNK and P38 signaling pathways (16). A deleterious role for SR-BI has also been reported in granulocytes.…”

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confidence: 99%

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Adrenocortical Scavenger Receptor Class B Type I Deficiency Exacerbates Endotoxic Shock and Precipitates Sepsis-Induced Mortality in Mice

Gilibert

Galle-Treger

Moreau

et al. 2014

The Journal of Immunology

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Scavenger receptor class B type I (SR-BI)–deficient mice display reduced survival to endotoxic shock and sepsis. The understanding of the mechanisms underlying SR-BI protection has been hampered by the large spectrum of SR-BI functions and ligands. It notably plays an important role in the liver in high-density lipoprotein metabolism, but it is also thought to participate in innate immunity as a pattern recognition receptor for bacterial endotoxins, such as LPS. In this study, we sought to determine the tissue-specific contribution of SR-BI in the hyperinflammatory response and high mortality rates observed in SR-BI−/− mice in endotoxicosis or sepsis. Restoring plasma levels of high-density lipoprotein, which are critical lipoproteins for LPS neutralization, did not improve acute outcomes of LPS injection in SR-BI−/− mice. Mice deficient for SR-BI in hepatocytes, endothelial cells, or myeloid cells were not more susceptible to LPS-induced death. However, if SR-BI ablation in hepatocytes led to a moderate increase in systemic inflammatory markers, SR-BI deficiency in myeloid cells was associated with an anti-inflammatory effect. Finally, mice deficient for SR-BI in the adrenal cortex, where the receptor provides lipoprotein-derived cholesterol, had impaired secretion of glucocorticoids in response to stress. When exposed to an endotoxin challenge, these mice exhibited an exacerbated systemic and local inflammatory response, reduced activation of atrophy genes in muscle, and high lethality rate. Furthermore, polymicrobial sepsis induced by cecal ligature and puncture resulted in early death of these animals. Our study clearly demonstrates that corticoadrenal SR-BI is a critical element of the hypothalamic-pituitary-adrenal axis to provide effective glucocorticoid-dependent host defense after an endotoxic shock or bacterial infection.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

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Adrenocortical Scavenger Receptor Class B Type I Deficiency Exacerbates Endotoxic Shock and Precipitates Sepsis-Induced Mortality in Mice

Gilibert

Galle-Treger

Moreau

et al. 2014

The Journal of Immunology

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“…SR-BI is moderately expressed in macrophages and recent studies demonstrated that macrophage SR-BI suppresses inflammatory response of macrophages to LPS (50,52). To test whether a deficiency of hepatic SR-BI affects inflammatory response in macrophages, we utilized bone marrow-derived macrophages from Scarb1 I179N and control mice.…”

Section: Hepatic Sr-bi Protects Against Clp-induced Septic Death-mentioning

confidence: 99%

Hepatic Scavenger Receptor BI Protects Against Polymicrobial-induced Sepsis through Promoting LPS Clearance in Mice

Guo

Zheng

Ai³

et al. 2014

Journal of Biological Chemistry

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Background: We utilized Scarb1I179N mice, a model deficient in hepatic SR-BI, to determine the role of hepatic SR-BI in sepsis. Results: Upon cecal ligation and puncture (CLP), Scarb1 I179N mice had a 3.5-fold increase in fatality associated with an impaired LPS clearance. Conclusion: Hepatic SR-BI protects against sepsis through promoting LPS clearance. Significance: Promoting hepatic SR-BI-mediated LPS clearance may provide a therapeutic approach for sepsis.

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“…Bone marrow-specific deficiency of SR-BI in both apoE knockout and LDLR knockout mice increases atherosclerosis in the aorta. 15,26,27 Conversely, we have recently shown that restoring SR-BI expression in the bone marrow of SR-BI knockout/apoE hypomorphic mice reduces diet-induced occlusive CA atherosclerosis, whereas others have shown that transplanting SR-BI/apoE dKO mice with wild-type bone marrow has a similar effect.28,29 SR-BI in macrophages reduces the inflammatory response to lipopolysaccharide treatment in vitro, 30 and SR-BI deficiency is associated with higher serum cytokine levels in naïve, septic, and lipopolysaccharide-challenged mice. [31][32][33] Results from the current study show that SR-BI/LDLR dKO mice challenged with atherogenic diets have increased levels of both IL-6 and TNFα in plasma, accompanied by increased numbers of both monocytes and lymphocytes in blood compared with LDLR knockout mice fed the same diets.…”

mentioning

confidence: 99%

The Effects of Diet on Occlusive Coronary Artery Atherosclerosis and Myocardial Infarction in Scavenger Receptor Class B, Type 1/Low-Density Lipoprotein Receptor Double Knockout Mice

Fuller

Dadoo

Serkis

et al. 2014

ATVB

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The HDL receptor, scavenger receptor class B type I (SR-BI), is expressed on the surface of multiple cell types and has been shown to mediate both HDL-dependent atheroprotective © 2014 American Heart Association, Inc.Arterioscler Thromb Vasc Biol is available at http://atvb.ahajournals.org DOI: 10.1161/ATVBAHA.114.304200Objective-Deficiency of the high-density lipoprotein receptor, scavenger receptor class B, type I (SR-BI), in apolipoprotein E knockout or hypomorphic mice, respectively, results in spontaneous or diet-inducible occlusive coronary artery (CA) atherosclerosis, myocardial infarction, and early death. Here, we examine effects of SR-BI deficiency on cardiovascular phenotypes in low-density lipoprotein receptor (LDLR) knockout mice fed different atherogenic diets. Approach and Results-SR-BI/LDLR double knockout and control LDLR knockout mice were fed atherogenic diets containing different amounts of fat, cholesterol, and sodium cholate. Double knockout mice fed atherogenic diets high in cholesterol exhibited significantly reduced survival compared with LDLR knockout mice fed the same diets. In addition to increased diet-accelerated aortic sinus atherosclerosis, we observed significant diet-induced CA atherosclerosis in double knockout mice and diet-dependent accumulation of platelets in CA atherosclerotic plaques. This was accompanied by substantial myocardial fibrosis in double knockout mice fed high cholesterol diets. Atherogenic diet fed double knockout mice also exhibited higher circulating cytokine levels, monocytosis with increased proportions of Ly6C hi and Ly6C int monocytes, and higher adhesion molecule expression in CA endothelial cells compared with control LDLR knockout mice. Conclusions-Diet-accelerated atherosclerosis and occlusive, platelet-rich CA disease in SR-BI/LDLR double knockout mice is affected by amounts of cholesterol and cholate in atherogenic diets and is accompanied by increased expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 in CAs and increased Ly6C hi and Ly6C Fuller et al Coronary Atherosclerosis in SR-BI/LDLR dKO Mice 2395signaling 8,9 and selective lipid transfer between HDL and cells, which is critical for functional reverse cholesterol transport, the major avenue for cholesterol removal from peripheral tissues.8,10 Deficiency of SR-BI not only accelerates atherosclerosis in the aortic sinus of apoE knockout mice 11 but also renders these mice susceptible to spontaneous occlusive CA atherosclerosis, myocardial infarction, and ultimately early death. 12 A related model, the SR-BI knockout/apoE hypomorphic mouse, develops a similar phenotype when fed high fat, high cholesterol (HFC) diets. 13,14 We have previously shown that SR-BI deficiency increases atherosclerosis in the aortas of LDLR knockout mice fed a high-fat (HF) Western-type diet; however, reduced survival was not observed in these mice, and CA atherosclerosis was not assessed. 15In the current study, we tested the effects of feeding SR-BI/ LDLR double knockout (dKO) mic...

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Macrophage SR-BI regulates LPS-induced pro-inflammatory signaling in mice and isolated macrophages

Cited by 59 publications

References 43 publications

Adrenocortical Scavenger Receptor Class B Type I Deficiency Exacerbates Endotoxic Shock and Precipitates Sepsis-Induced Mortality in Mice

Adrenocortical Scavenger Receptor Class B Type I Deficiency Exacerbates Endotoxic Shock and Precipitates Sepsis-Induced Mortality in Mice

Hepatic Scavenger Receptor BI Protects Against Polymicrobial-induced Sepsis through Promoting LPS Clearance in Mice

The Effects of Diet on Occlusive Coronary Artery Atherosclerosis and Myocardial Infarction in Scavenger Receptor Class B, Type 1/Low-Density Lipoprotein Receptor Double Knockout Mice

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