Low-Density Lipoprotein Receptor Deficiency Attenuates Neuroinflammation through the Induction of Apolipoprotein E

Mailleux, Jo; Timmermans, Silke; Nelissen, Katherine; Vanmol, Jasmine; Vanmierlo, Tim; Horssen, Jack van; Bogie, Jeroen F. J.; Hendriks, Jerome J. A.

doi:10.3389/fimmu.2017.01701

Cited by 18 publications

(20 citation statements)

References 49 publications

(42 reference statements)

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“…From our study, we found PAI-1 increased in WT mice exposed to PG with nicotine, but this increase was significantly reduced in KO mice, indicating that the SKIL-TGFβ-PAI-1 connection may be regulated by nAChR α7 when challenged with e-cig aerosol containing nicotine. In relation to the other significantly altered target, LDLR, previous publications have proved that it is related to inflammatory processes [40,41]. Ricci et al identified that LDLR is associated with macrophage differentiation [40]; and that LDLR deficiency is capable of reducing inflammatory responses in THP-1 cells [40], as well as inhibiting the pro-inflammatory cytokines in the central nervous system [41].…”

Section: Discussionmentioning

confidence: 99%

“…In relation to the other significantly altered target, LDLR, previous publications have proved that it is related to inflammatory processes [40,41]. Ricci et al identified that LDLR is associated with macrophage differentiation [40]; and that LDLR deficiency is capable of reducing inflammatory responses in THP-1 cells [40], as well as inhibiting the pro-inflammatory cytokines in the central nervous system [41]. In our study, downregulation of LDLR was seen in PG with nicotine exposed WT mice while this effect was significantly reduced in mice with the nAChR α7 deletion.…”

Section: Discussionmentioning

confidence: 99%

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E-cigarette-Induced Pulmonary Inflammation and Dysregulated Repair are Mediated by nAChR α7 Receptor

Wang¹,

Sundar²,

Li³

et al. 2020

Preprint

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Electronic cigarette (e-cig) vaping is increasing rapidly in the United States, as e-cigs are considered less harmful than combustible cigarettes. However, limited research has conducted to understand the mechanism of toxicological and pulmonary effects of e-cigs. We hypothesized that sub-chronic exposure of e-cigs induced inflammatory response and dysregulated repair/extracellular matrix (ECM) remodeling, which occur through the α7 nicotinic acetylcholine receptor (nAChR α7). Adult wild-type (WT), nAChRα7 knockout (KO), and lung epithelial-cell-specific KO (nAChRα7 CreCC10) mice were exposed to e-cig aerosol containing propylene glycol (PG) with or without nicotine. Bronchoalveolar lavage fluids (BALF) and lungs were collected for determination of inflammatory responses and ECM remodeling, respectively. Sub-chronic e-cig exposure with nicotine increased the lung influx of macrophages and T-lymphocytes, and the levels of pro-inflammatory cytokines, while nAChR α7 knockdown blocked the inflammatory responses. Interestingly, matrix metalloproteinases (MMPs), such as MMP2, MMP8, and MMP9, in both sex mice were altered at both protein and gene levels when WT mice were exposed to PG alone in a sex-dependent manner. Moreover, MMP12 increased significantly in male mice exposed to PG with or without nicotine in a nAChR α7 dependent manner.Additionally, the abundance of ECM proteins, such as collagen and fibronectin, was significantly altered after sub-chronic e-cig exposure with or without nicotine in a sex-dependent manner, but nAChR α7 independent manner. Overall, sub-chronic e-cig exposure with or without nicotine affected lung inflammation and repair responses/ECM remodeling, which were mediated by nAChR α7 in a sexdependent manner. electronic cigarette aerosol and inhaled nicotine effects on periodontal and pulmonary tissues. Oral Dis 2017, 23:1052-1057. 3. Kaur G, Muthumalage T, Rahman I: Mechanisms of toxicity and biomarkers of flavoring and flavor enhancing chemicals in emerging tobacco and nontobacco products. Toxicol Lett 2018, 288:143-155.4.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

E-cigarette-Induced Pulmonary Inflammation and Dysregulated Repair are Mediated by nAChR α7 Receptor

Wang¹,

Sundar²,

Li³

et al. 2020

Preprint

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“…Endogenous APOE and exogenous APOE mimetic peptides reduced glial activation and inflammatory cytokines release after CNS disease. Interestingly, blocking inflammatory signaling effectively increases APOE expression in neuroinflammatory processes (Pocivavsek and Rebeck, 2009 ; Mailleux et al, 2017 ). These evidences suggest that APOE production and inflammation are in a negative feedback loop, with APOE suppressing inflammation and inflammation suppressing APOE production.…”

Section: Discussionmentioning

confidence: 99%

Apolipoprotein E Deficiency Exacerbates Spinal Cord Injury in Mice: Inflammatory Response and Oxidative Stress Mediated by NF-κB Signaling Pathway

Yang

Chen²,

Shao³

et al. 2018

Front. Cell. Neurosci.

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Spinal cord injury (SCI) is a severe neurological trauma that involves complex pathological processes. Inflammatory response and oxidative stress are prevalent during the second injury and can influence the functional recovery of SCI. Specially, Apolipoprotein E (APOE) induces neuronal repair and nerve regeneration, and the deficiency of Apoe impairs spinal cord-blood-barrier and reduces functional recovery after SCI. However, the mechanism by which Apoe mediates signaling pathways of inflammatory response and oxidative stress in SCI remains largely elusive. This study was designed to investigate the signaling pathways that regulate Apoe deficiency-dependent inflammatory response and oxidative stress in the acute stage of SCI. In the present study, Apoe−/− mice retarded functional recovery and had a larger lesion size when compared to wild-type mice after SCI. Moreover, deficiency of Apoe induced an exaggerated inflammatory response by increasing expression of interleukin-6 (IL-6) and interleukin-1β (IL-1β), and increased oxidative stress by reducing expression of Nrf2 and HO-1. Furthermore, lack of Apoe promoted neuronal apoptosis and decreased neuronal numbers in the anterior horn of the spinal cord after SCI. Mechanistically, we found that the absence of Apoe increased inflammation and oxidative stress through activation of NF-κB after SCI. In contrast, an inhibitor of nuclear factor-κB (NF-κB; Pyrrolidine dithiocarbamate) alleviates these changes. Collectively, these results indicate that a critical role for activation of NF-κB in regulating Apoe-deficiency dependent inflammation and oxidative stress is detrimental to recovery after SCI.

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“…LXR activation decreases disease severity, Th17 polarization and IL-17 secretion in EAE, though certain oxysterols may have pro-inflammatory effects in these models [ 64 ]. The Mailleux group also reported that in EAE, LDL receptor deficiency attenuates the severity of the disease in females (not in males) mice, through the induction of ApoE [ 65 ]. Interestingly, other authors have found that, in ApoE knock-out mice, ApoE deficiency increases EAE severity only in female animals [ 8 ].…”

Section: Genesis and Repair Of Ms Lesionsmentioning

confidence: 99%

“…RRMS subjects have smaller LDL in comparison to healthy controls and in some cases increased levels of small HDL with impaired anti-inflammatory activity [ 88 ]. Interestingly, this study observed some differences between male and female patients, suggesting gender differences in lipid metabolism associated with MS [ 65 ]. Supporting this hypothesis, recent research from our group suggests that sex steroids modify the serum lipid profile associated with disability in these patients (unpublished results).…”

Section: Systemic Metabolism In Msmentioning

confidence: 99%

Metabolic Dysfunction and Peroxisome Proliferator-Activated Receptors (PPAR) in Multiple Sclerosis

Ferret-Sena

Capela

Sena

2018

IJMS

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Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease of the central nervous system (CNS) probably caused, in most cases, by the interaction of genetic and environmental factors. This review first summarizes some clinical, epidemiological and pathological characteristics of MS. Then, the involvement of biochemical pathways is discussed in the development and repair of the CNS lesions and the immune dysfunction in the disease. Finally, the potential roles of peroxisome proliferator-activated receptors (PPAR) in MS are discussed. It is suggested that metabolic mechanisms modulated by PPAR provide a window to integrate the systemic and neurological events underlying the pathogenesis of the disease. In conclusion, the reviewed data highlight molecular avenues of understanding MS that may open new targets for improved therapies and preventive strategies for the disease.

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Low-Density Lipoprotein Receptor Deficiency Attenuates Neuroinflammation through the Induction of Apolipoprotein E

Cited by 18 publications

References 49 publications

E-cigarette-Induced Pulmonary Inflammation and Dysregulated Repair are Mediated by nAChR α7 Receptor

E-cigarette-Induced Pulmonary Inflammation and Dysregulated Repair are Mediated by nAChR α7 Receptor

Apolipoprotein E Deficiency Exacerbates Spinal Cord Injury in Mice: Inflammatory Response and Oxidative Stress Mediated by NF-κB Signaling Pathway

Metabolic Dysfunction and Peroxisome Proliferator-Activated Receptors (PPAR) in Multiple Sclerosis

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