CoChat
Sign Up
Cited by 39Neuroinflammation and Neurodegeneration MechanismsNanoparticle-Based Drug DeliveryImmune Response and Inflammation

Lipopolysaccharide-QD Micelles Induce Marked Induction of TLR2 and Lipid Droplet Accumulation in Olfactory Bulb Microglia

Open access
Lalancette-Hébert, Mélanie, Moquin, Alexandre, Choi, Angela O., Kriz, Jasna, Maysinger, Dusica·2010·Molecular Pharmaceutics
DOI 10.1021/mp1000372
Open this paper in CoChat — free accountOpen PDF

Abstract

The intranasal entry of biological and artificial nanoparticles can induce inflammatory responses both locally and more widely in surrounding tissues. The aim of this study was to assess the microglia activation induced by nanoparticles with different surfaces in (i) a transgenic mouse (Toll-like receptor (TLR)-2-luciferase (Luc) reporter) which allowed the biophotonic imaging of microglial activation/innate immune response after intranasal delivery of nanoparticles and (ii) in microglial dispersed cells in vitro. Cadmium selenide nanoparticles (quantum dots, QD), surface-exchanged with lipopolysaccharide (LPS) to form micelles, were tested to assess microglia activation and lipid droplet formation in both model systems. In vivo imaging revealed a robust increase in the extent of microglial activation/TLR2 response, initially in the olfactory bulb, but also in other more caudal brain regions. The increased TLR2 expression was complemented with enhanced CD68 expression in activated microglia in the same regions. Intense in vitro microglial activation by LPS-QD micelles was accompanied by a significant enhancement of nitric oxide production and formation of large lipid droplets, suggesting the possibility of this organelle acting as an inflammatory biomarker in response to nanoparticles, and not simply as a storage site in fat tissues.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1021/mp1000372

Cites

4 of 4 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • LPS-mediated inflammation promotes lipid droplet accumulation in immune cells.

    “LPS mediated-inflammation is known to promote LD accumulation in immune cells [19,69,70].”

    From Lipoprotein Lipase Regulates Microglial Lipid Droplet Accumulation (2021) · cites this paper as [69]

    The Results section (page unavailable) reports that LPS exposure led to lipid-droplet formation in primary olfactory-bulb cultures, including microglia. But in N9 microglial cells, LPS alone did not significantly change droplet number or size; LPS-QD micelles produced fewer, larger droplets. The paper therefore does not establish the broader claim that LPS-mediated inflammation promotes lipid-droplet accumulation across immune cells. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 26

  1. Liu, C. H.; You, Z.; Ren, J.; Kim, Y. R.; Eikermann-Haerter, K.; Liu, P. K.; Noninvasive delivery of gene targeting probes to live brains for transcription MRI, FASEB J. 2008, 22 (4), 1193-203.
  2. Potter, W.; Kalil, R. E.; Kao, W. J. Biomimetic material systems for neural progenitor cell-based therapy. Front. Biosci. 2008, 13, 806-21.
  3. Au, C.; Mutkus, L.; Dobson, A.; Riffle, J.; Lalli, J.; Aschner, M. Effects of nanoparticles on the adhesion and cell viability on astrocytes. Biol. Trace Elem. Res. 2007, 120 (1-3), 248-56.
  4. Tsutsui, Y.; Tomizawa, K.; Nagita, M.; Michiue, H.; Nishiki, T.; Ohmori, I.; Seno, M.; Matsui, H. Development of bionanocapsules targeting brain tumors. J. Controlled Release 2007, 122 (2), 159- 64.
  5. Park, I. K.; Lasiene, J.; Chou, S. H.; Horner, P. J.; Pun, S. H. Neuron-specific delivery of nucleic acids mediated by Tet1- modified poly(ethylenimine). J. Gene Med. 2007, 9 (8), 691-702.
  6. Ribot, E.; Bouzier-Sore, A. K.; Bouchaud, V.; Miraux, S.; Delville, M. H.; Franconi, J. M.; Voisin, P. Microglia used as vehicles for both inducible thymidine kinase gene therapy and MRI contrast agents for glioma therapy. Cancer Gene Ther. 2007, 14 (8), 724- 37.
  7. Voisin, P.; Ribot, E. J.; Miraux, S.; Bouzier-Sore, A. K.; Lahitte, J. F.; Bouchaud, V.; Mornet, S.; Thiaudiere, E.; Franconi, J. M.; Raison, L.; Labrugere, C.; Delville, M. H. Use of lanthanide- grafted inorganic nanoparticles as effective contrast agents for cellular uptake imaging. Bioconjugate Chem. 2007, 18 (4), 1053- 63. articles
  8. Shin, J. A.; Lee, E. J.; Seo, S. M.; Kim, H. S.; Kang, J. L.; Park, E. M. Nanosized titanium dioxide enhanced inflammatory re- sponses in the septic brain of mouse. Neuroscience 2010, 165 (2), 445-54.
  9. Al-Ghananeem, A. M.; Saeed, H.; Florence, R.; Yokel, R. A.; Malkawi, A. H. Intranasal drug delivery of didanosine-loaded chitosan nanoparticles for brain targeting; an attractive route against infections caused by AIDS viruses. J. Drug Targeting 2010, 18 (5), 381-8.
  10. Mistry, A.; Glud, S. Z.; Kjems, J.; Randel, J.; Howard, K. A.; Stolnik, S.; Illum, L. Effect of physicochemical properties on intranasal nanoparticle transit into murine olfactory epithelium. J. Drug Targeting 2009, 17 (7), 543-52.
  11. Hutter, E.; Boridy, S.; Labrecque, S.; Lalancette-Hebert, M.; Kriz, J.; Winnik, F. M.; Maysinger, D. Microglial Response to Gold Nanoparticles. ACS Nano 2010, DOI 10.1021/nn901869f. · DOI
  12. Olson, J. K.; Miller, S. D. Microglia initiate central nervous system innate and adaptive immune responses through multiple TLRs. J. Immunol. 2004, 173 (6), 3916-24.
  13. Lehnardt, S.; Lehmann, S.; Kaul, D.; Tschimmel, K.; Hoffmann, O.; Cho, S.; Krueger, C.; Nitsch, R.; Meisel, A.; Weber, J. R. Toll-like receptor 2 mediates CNS injury in focal cerebral ischemia. J. Neuroimmunol. 2007, 190 (1-2), 28-33.
  14. Trinchieri, G.; Sher, A. Cooperation of Toll-like receptor signals in innate immune defence. Nat. ReV. Immunol. 2007, 7 (3), 179- 90.
  15. Ziegler, G.; Harhausen, D.; Schepers, C.; Hoffmann, O.; Rohr, C.; Prinz, V.; Konig, J.; Lehrach, H.; Nietfeld, W.; Trende- lenburg, G. TLR2 has a detrimental role in mouse transient focal cerebral ischemia. Biochem. Biophys. Res. Commun. 2007, 359 (3), 574-9.
  16. Schwandner, R.; Dziarski, R.; Wesche, H.; Rothe, M.; Kirschning, C. J. Peptidoglycan-and lipoteichoic acid-induced cell activation is mediated by toll-like receptor 2. J. Biol. Chem. 1999, 274 (25), 17406-9.
  17. Underhill, D. M.; Ozinsky, A.; Hajjar, A. M.; Stevens, A.; Wilson, C. B.; Bassetti, M.; Aderem, A. The Toll-like receptor 2 is recruited to macrophage phagosomes and discriminates between pathogens. Nature 1999, 401 (6755), 811-5.
  18. Yoshimura, A.; Lien, E.; Ingalls, R. R.; Tuomanen, E.; Dziarski, R.; Golenbock, D. Cutting edge: recognition of Gram-positive bacterial cell wall components by the innate immune system occurs via Toll-like receptor 2. J. Immunol. 1999, 163 (1), 1-5.
  19. Letiembre, M.; Liu, Y.; Walter, S.; Hao, W.; Pfander, T.; Wrede, A.; Schulz-Schaeffer, W.; Fassbender, K. Screening of innate immune receptors in neurodegenerative diseases: a similar pattern. Neurobiol. Aging 2009, 30 (5), 759-68.
  20. Liu, Y.; Hao, W.; Dawson, A.; Liu, S.; Fassbender, K. Expression of amyotrophic lateral sclerosis-linked SOD1 mutant increases the neurotoxic potential of microglia via TLR2. J. Biol. Chem. 2009, 284 (6), 3691-9.
  21. Laflamme, N.; Soucy, G.; Rivest, S. Circulating cell wall components derived from Gram-negative, not Gram-positive, bacteria cause a profound induction of the gene-encoding Toll- like receptor 2 in the CNS. J. Neurochem. 2001, 79 (3), 648-57.
  22. Nguyen, M. D.; Julien, J. P.; Rivest, S. Innate immunity: the missing link in neuroprotection and neurodegeneration. Nat. ReV. Neurosci. 2002, 3 (3), 216-27.
  23. Taylor, D. L.; Pirianov, G.; Holland, S.; McGinnity, C. J.; Norman, A. L.; Reali, C.; Diemel, L. T.; Gveric, D.; Yeung, D.; Mehmet, H. Attenuation of proliferation in oligodendrocyte precursor cells by activated microglia. J. Neurosci. Res. 2010, 88 (8), 1632-44.
  24. Murphy, S.; Martin, S.; Parton, R. G. Lipid droplet-organelle interactions; sharing the fats. Biochim. Biophys. Acta 2009, 1791 (6), 441-7.
  25. Bozza, P. T.; Magalhaes, K. G.; Weller, P. F. Leukocyte lipid bodies -Biogenesis and functions in inflammation. Biochim. Biophys. Acta 2009, 1791 (6), 540-51.
  26. Martin, S.; Parton, R. G. Lipid droplets: a unified view of a dynamic organelle. Nat. ReV. Mol. Cell Biol. 2006, 7 (5), 373-8.

Cited by

Sorted by citations

Authors
Lalancette-Hébert, M., Moquin, A., Choi, A. O., Kriz, J., & Maysinger, D.
Affiliations
  • Department of Psychiatry and Neuroscience, Centre de Recherche du CHUL, Faculty of Medicine, Laval University, Quebec, QC, Canada, Faculty of Pharmacy and Department of Chemistry, Université de Montreal, Montreal, QC, Canada, and Department of Pharmacology and Therapeutics, Faculty of Medicine, McGill University, Montreal, QC, Canada
  • Université Laval (CA)
Venue
Molecular Pharmaceutics
Publisher
American Chemical Society (ACS)
Published
2010-05-21
Volume
7
Issue
4
Pages
1183-1194
ISSN
  • 1543-8384 (ISSN-L)
  • 1543-8392
DOI
10.1021/mp1000372
OpenAlex
W2075676578
Cited by
39
References
4
Citations by year
2026: 1 · 2025: 1 · 2024: 4 · 2021: 5 · 2020: 2 · 2019: 2 · 2018: 2 · 2017: 1 · 2016: 3 · 2015: 3 · 2013: 5 · 2012: 7
FWCI
2.90
Type
journal article
Language
en
Open access
Locations
  • Molecular Pharmaceutics (publishedVersion)
  • PubMed (publishedVersion)
  • eScholarship@McGill (McGill) (submittedVersion)
Funders
  • Canadian Institutes of Health Research
  • Natural Sciences and Engineering Research Council of Canada
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords
microglial activation, TLR2, lipid droplets, olfactory bulb, CdSe quantum dots, biophotonic imaging, nitric oxide production, CD68, neuroinflammation, inflammatory markers
MeSH terms
CD68 Molecule, Administration, Intranasal, Animals, Cell Line, Immunohistochemistry, Lipopolysaccharides, Mice, Transgenic, Micelles, Nitric Oxide, Olfactory Bulb, Antigens, Differentiation, Myelomonocytic, Antigens, CD, Microglia, Selenium Compounds, Cadmium Compounds, Lipid Metabolism, Toll-Like Receptor 2, Mice, Nanoparticles

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review