Carbon-based nanomaterials trigger inflammasome activation in human macrophages: role of toll-like receptor activation and intracellular sensing via NLRP3

Details

• Personal Author:
  Andon F ; Bhattacharya K ; Fadeel B ; Gessner I ; Kostarelos K ; Lozano N ; Mathur S ; Mukherjee SP ; Shvedova AA
• Description:
  Carbon-based nanomaterials (CBNs) hold great promises in the fields of medicine and engineering due to their intrinsic electro-mechanical properties (Bhattacharya et al. Nanomedicine. 2016;12(2):333-51). However, CBNs may also trigger inflammation leading to potential adverse outcomes. Inflammasomes are key signaling platforms that detect microorganisms as well as sterile stressors, leading to the secretion of pro-inflammatory cytokines, e.g., IL-1beta. Here we investigated how different CBNs, including hollow carbon spheres (HCS), single- and multi-walled carbon nanotubes (CNTs), and graphene oxides (GO; with small or large lateral dimensions) are sensed by primary human macrophages which are key cells of the innate immune system. First, we determined the endotoxin content of all the materials, a prerequisite for any studies using immune-competent cells. Then, primary human monocyte-derived macrophages (HMDM) were exposed for 24 h of the various CBNs to assess cytotoxicity. We also performed cytokine profiling using a multiplex assay, and IL-1beta secretion was monitored using ELISA, in HMDMs primed or not with lipopolysaccharide (LPS). IL-1beta production was noted in presence, but not in the absence of LPS priming, indicative of inflammasome activation. Using THP-1 knockdown cell lines, we found that IL-1beta secretion was caspase-1-, ASC-, and NLRP3- dependent. Furthermore, HEK293 reporter cell lines were employed to evaluate the role of Toll-like receptor activation. Notably, SWCNT were apparently sensed by both TLR 2 and TLR4, while GO did not trigger TLR activation. Overall, our study showed that different CBNs, both small, spherical carbon particles (i.e., HCS) as well as small and large GOs, and CNTs, are capable of activating inflammasome, but only when the macrophages are LPS primed. [Description provided by NIOSH]
• Subjects:
  Blood Cytotoxins Endotoxins Enzymes Immune System Lipids Macrophages Microbiology Occupational Health Particulate Matter Safety Toxicology

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• Keywords:
  Carbon Carbon Nanotubes Cell Signaling Cellular Effects Cellular Reactions Cytokines Cytotoxicity ELISA Enzyme-linked Immunosorbent Assay Enzyme Activity Exposure Assessment Graphene Graphene Oxide Humans Immune Reaction Immune System Lipopolysaccharide Microorganisms Multi-walled Carbon Nanotubes MWCNT Nanomaterials Nanotechnology Nanotoxicology Nanotubes Oxides Particle Size Single-walled Carbon Nanotubes SWCNT

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Maryland ; OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  156
• Issue:
  1
• NIOSHTIC Number:
  nn:20049466
• Citation:
  Toxicologist 2017 Mar; 156(1):401
• CAS Registry Number:
  Carbon (CAS RN 7440-44-0) ; Carbon nanotubes (CAS RN 308068-56-6) ; Graphene (CAS RN 1034343-98-0)
• Federal Fiscal Year:
  2017
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 56th Annual Meeting and ToxExpo, March 12-16, 2017, Baltimore, Maryland
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:8e2848d9cdc4cbdcd52286c00bfe353a190a5af222968077cb0ce3b1535f0b70cb287635526b4b2a6119cc7691dff607246c9eeeb77053cb4e8cc6038223ad8c
• Download URL:
  https://stacks.cdc.gov/view/cdc/203910/cdc_203910_DS1.pdf
• File Type:
  [PDF - 943.77 KB ]