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Low‐density lipoprotein receptors regulate microglial inflammation through c‐Jun N‐terminal kinase
Abstract
Apolipoprotein E (apoE) has been implicated in modulating the central nervous system (CNS) inflammatory response. However, the molecular mechanisms involved in apoE‐dependent immunomodulation are poorly understood. We hypothesize that apoE alters the CNS inflammatory response by signaling via low‐density lipoprotein (LDL) receptors in glia. To address this hypothesis, we used a small bioactive peptide formed from the receptor‐binding domain of apoE, apoE peptide (EP), to study LDL receptor signaling in microglia. To model glial activation, we treated primary mouse microglia and the microglial cell line BV2 with lipopolysaccharide (LPS) and studied two inflammatory responses: an increase in nitric oxide production (NO) and a decrease in apoE production. We found that treatment of primary microglia and BV2 cells with EP attenuated LPS‐induced NO accumulation and apoE reduction in a dose‐dependent manner. Using the receptor‐associated protein to block ligand binding to members of the LDL receptor family, we found that EP attenuated both of these LPS‐induced inflammatory responses via LDL receptors. We studied two intracellular signaling cascades associated with apoE: c‐Jun N‐terminal kinase (JNK) and extracellular signal‐regulated kinase (ERK). LPS induced both ERK and JNK activation, whereas EP induced ERK activation, but drastically reduced JNK activation. Inhibition of JNK with SP600125 reduced LPS‐induced NO production and apoE reduction in a dose‐dependent manner. Treatment of microglia with suboptimal EP in combination with JNK inhibitor enhanced attenuation of LPS‐induced NO production. These data suggest that microglial LDL receptors regulate JNK activation, which is necessary for apoE modulation of the inflammatory response. © 2008 Wiley‐Liss, Inc.
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APOE4 is associated with increased innate immune reactivity and enhanced cytokine secretion in primary microglia and peripheral macrophages in various animal models as well as human subjects.
“Recently, several studies have shown that APOE4 is associated with increased innate immune reactivity and enhanced cytokine secretion in primary microglia and peripheral macrophages in various animal models as well as human subjects [31–42].”
From 25-Hydroxycholesterol amplifies microglial IL-1β production in an apoE isoform-dependent manner (2020) · cites this paper as [38]
The Introduction (page not provided) says apoE modulates CNS inflammation in an isoform-specific manner. The study’s microglial findings concern an apoE-derived peptide and nitric oxide production, not an APOE4-specific increase in cytokine secretion. Our copy does not establish the claimed findings in peripheral macrophages or human subjects. (LLM, conf=0.84)
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Cites
The phosphoinositide 3-kinase pathway
Cantley, L. C. (2002) · Science · doi:10.1126/science.296.5573.1655 · Cited by 5,621
Apolipoprotein E: Structure-Function Relationships
Weisgraber, K. H. (1994) · Advances in Protein Chemistry · doi:10.1016/s0065-3233(08)60642-7 · Cited by 830
Boyles, J. K., Pitas, R. E., Wilson, E., Mahley, R. W., & Taylor, J. M. (1985) · Journal of Clinical Investigation · doi:10.1172/jci112130 · Cited by 829
Synuclein activates microglia in a model of Parkinson's disease
Su, X., Maguire-Zeiss, K. A., Giuliano, R., Prifti, L., Venkatesh, K., & Federoff, H. J. (2008) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.04.006 · Cited by 474 · cited 1×
“Primary mouse microglial cell cultures were prepared from postnatal day 1 Swiss-Webster mouse pups using a slightly modified method from that of Su et al. (2008).”
MethodLynch, J. R., Tang, W., Wang, H., Vitek, M. P., Bennett, E. R., Sullivan, P. M., Warner, D. S., & Laskowitz, D. T. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m306923200 · Cited by 394
The reelin receptor ApoER2 recruits JNK-interacting proteins-1 and -2
Stockinger, W., Brandes, C., Fasching, D., Hermann, M., Gotthardt, M., Herz, J., Schneider, W. J., & Nimpf, J. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m004119200 · Cited by 239 · cited 1×
“Of particular relevance to this study, the cytoplasmic domain of LRP1 binds JNK-interacting proteins (JIP-1 and JIP-2) (Stockinger et al., 2000).”
BackgroundApolipoprotein E Receptors Mediate the Effects of β-Amyloid on Astrocyte Cultures
LaDu, M. J., Shah, J. A., Reardon, C. A., Getz, G. S., Bu, G., Hu, J., Guo, L., & Van Eldik, L. J. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m000602200 · Cited by 103
Flagged first, then by citations
Research works printed but not linked: 47
- 10.1038/35021228 · DOI
- 10.1194/jlr.R300017-JLR200 · DOI
- 10.1523/JNEUROSCI.18-05-01633.1998 · DOI
- 10.1016/0165-5728(90)90073-V · DOI
- 10.4049/jimmunol.149.8.2736 · DOI
- 10.1097/00005072-199604000-00012 · DOI · Paper page
- 10.1002/glia.440070309 · DOI
- 10.1126/science.277.5326.693 · DOI · Paper page
- Dory L, 1993, Post‐transcriptional regulation of apolipoprotein E expression in mouse macrophages by phorbol ester, Biochem J, 292, 105, 10.1042/bj2920105 · DOI
- 10.1074/jbc.M611422200 · DOI
- 10.1074/jbc.M000955200 · DOI · Paper page
- 10.1016/S0304-3940(02)00218-5 · DOI
- 10.1016/S0006-2952(02)01139-5 · DOI
- 10.1111/j.1471-4159.2004.03007.x · DOI · Paper page
- 10.1016/j.brainres.2006.07.035 · DOI · Paper page
- 10.1074/jbc.271.14.8373 · DOI · Paper page
- 10.1016/S0197-0186(01)00050-X · DOI · Paper page
- 10.1016/S0165-5728(97)00021-0 · DOI · Paper page
- 10.1016/S0022-2275(20)32409-3 · DOI
- 10.1097/00001756-199803090-00010 · DOI
- 10.1006/exnr.2001.7541 · DOI · Paper page
- 10.1172/JCI8541 · DOI
- 10.1016/S0165-5728(00)00459-8 · DOI
- 10.1179/016164107X158974 · DOI
- 10.1093/oxfordjournals.jbchem.a122882 · DOI
- 10.1007/BF00353892 · DOI
- 10.1016/j.intimp.2007.04.005 · DOI
- 10.1074/jbc.M311841200 · DOI · Paper page
- Mouchel Y, 1995, Apolipoprotein E gene expression in astrocytes: Developmental pattern and regulation, Neuroreport, 7, 205
- 10.1172/JCI113568 · DOI
- 10.1016/j.nbd.2005.05.002 · DOI
- 10.1089/ars.2006.8.903 · DOI
- 10.1016/0169-328X(91)90111-A · DOI
- 10.1097/00001756-199803300-00020 · DOI
- 10.1016/0896-6273(93)90070-8 · DOI · Paper page
- 10.1089/ars.2006.8.929 · DOI
- 10.1046/j.1471-4159.2003.01788.x · DOI
- 10.1002/(SICI)1098-1136(199803)22:3<295::AID-GLIA8>3.0.CO;2-4 · DOI
- 10.1111/j.1471-4159.1992.tb08328.x · DOI
- 10.1073/pnas.90.5.1977 · DOI · Paper page
- 10.1073/pnas.85.24.9821 · DOI
- 10.1074/jbc.273.50.33556 · DOI · Paper page
- Vitek MP, 2008, APOE genotype‐specific differences in the innate immune response, Neurobiol Aging
- 10.1101/gad.922801 · DOI · Paper page
- 10.1074/jbc.M207324200 · DOI
- 10.1002/glia.10314 · DOI
- 10.1002/jlb.55.6.743 · DOI
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Yu, J.-T., Tan, L., & Hardy, J. (2014) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-071013-014300 · Cited by 394
Lipid and Lipoprotein Metabolism in Microglia
Loving, B. A., & Bruce, K. D. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.00393 · Cited by 255
APOE genotype alters glial activation and loss of synaptic markers in mice
Zhu, Y., Nwabuisi‐Heath, E., Dumanis, S. B., Tai, L. M., Yu, C., Rebeck, G. W., & Ladu, M. J. (2012) · Glia · doi:10.1002/glia.22289 · Cited by 224
Self-citationHuman APOE4 increases microglia reactivity at Aβ plaques in a mouse model of Aβ deposition
Rodriguez, G. A., Tai, L. M., LaDu, M. J., & Rebeck, G. W. (2014) · Journal of Neuroinflammation · doi:10.1186/1742-2094-11-111 · Cited by 193
Self-citationTai, L. M., Ghura, S., Koster, K. P., Liakaite, V., Maienschein‐Cline, M., Kanabar, P., Collins, N., Ben‐Aissa, M., Lei, A. Z., Bahroos, N., et al. (2015) · Journal of Neurochemistry · doi:10.1111/jnc.13072 · Cited by 165
Genetics ignite focus on microglial inflammation in Alzheimer’s disease
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Self-citation25-Hydroxycholesterol amplifies microglial IL-1β production in an apoE isoform-dependent manner
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JNK and NADPH oxidase involved in fluoride-induced oxidative stress in BV-2 microglia cells
Yan, L., Liu, S., Wang, C., Wang, F., Song, Y., Yan, N., Xi, S., Liu, Z., & Sun, G. (2013) · Mediators of Inflammation · doi:10.1155/2013/895975 · Cited by 58
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Tamboli, I. Y., Heo, D., & Rebeck, G. W. (2014) · PLoS ONE · doi:10.1371/journal.pone.0093120 · Cited by 35
Self-citationApoE mimetic peptide decreases Aβ production in vitro and in vivo
Minami, S. S., Cordova, A., Cirrito, J. R., Tesoriero, J. A., Babus, L. W., Davis, G. C., Dakshanamurthy, S., Turner, R. S., Pak, D. T., Rebeck, G. W., et al. (2010) · Molecular Neurodegeneration · doi:10.1186/1750-1326-5-16 · Cited by 34
Self-citation
Metadata
- Authors
- Pocivavsek, A., Burns, M. P., & Rebeck, G. W.
- Venue
- Glia
- Publisher
- Wiley
- Published
- 2008-09-19
- Volume
- 57
- Issue
- 4
- Pages
- 444-453
- ISSN
- 0894-1491
- 1098-1136
- PMC
- PMC2628955
- Cited by
- 96
- References
- 7
- Language
- en
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