In Vitro Inflammation and Toxicity Assessment of Pre- and Post-Incinerated Organomodified Nanoclays to Macrophages Using High-Throughput Screening Approaches

Details

• Personal Author:
  Agarwal S ; Coyle JP ; Derk R ; Dinu CZ ; Dozier, Alan K. ; Friend SA ; Gupta RK ; Jensen J ; Kornberg TG ; Rojanasakul LW ; Stueckle, Todd A. ; Wagner A
• Description:
  Background: Organomodified nanoclays (ONC), two-dimensional montmorillonite with organic coatings, are increasingly used to improve nanocomposite properties. However, little is known about pulmonary health risks along the nanoclay life cycle even with increased evidence of airborne particulate exposures in occupational environments. Recently, oropharyngeal aspiration exposure to pre- and post-incinerated ONC in mice caused low grade, persistent lung inflammation with a pro-fibrotic signaling response with unknown mode(s) of action. We hypothesized that the organic coating presence and incineration status of nanoclays determine the inflammatory cytokine secretary profile and cytotoxic response of macrophages. To test this hypothesis differentiated human macrophages (THP-1) were acutely exposed (0-20 µg/cm2) to pristine, uncoated nanoclay (CloisNa), an ONC (Clois30B), their incinerated byproducts (I-CloisNa and I-Clois30B), and crystalline silica (CS) followed by cytotoxicity and inflammatory endpoints. Macrophages were co-exposed to lipopolysaccharide (LPS) or LPS-free medium to assess the role of priming the NF-kB pathway in macrophage response to nanoclay treatment. Data were compared to inflammatory responses in male C57Bl/6J mice following 30 and 300 µg/mouse aspiration exposure to the same particles. Results: In LPS-free media, CloisNa exposure caused mitochondrial depolarization while Clois30B exposure caused reduced macrophage viability, greater cytotoxicity, and significant damage-associated molecular patterns (IL-1a and ATP) release compared to CloisNa and unexposed controls. LPS priming with low CloisNa doses caused elevated cathepsin B/Caspage-1/IL-1β release while higher doses resulted in apoptosis. Clois30B exposure caused dose-dependent THP-1 cell pyroptosis evidenced by Cathepsin B and IL-1β release and Gasdermin D cleavage. Incineration ablated the cytotoxic and inflammatory effects of Clois30B while I-CloisNa still retained some mild inflammatory potential. Comparative analyses suggested that in vitro macrophage cell viability, inflammasome endpoints, and pro-inflammatory cytokine profiles significantly correlated to mouse bronchioalveolar lavage inflammation metrics including inflammatory cell recruitment. Conclusions: Presence of organic coating and incineration status influenced inflammatory and cytotoxic responses following exposure to human macrophages. Clois30B, with a quaternary ammonium tallow coating, induced a robust cell membrane damage and pyroptosis effect which was eliminated after incineration. Conversely, incinerated nanoclay exposure primarily caused elevated inflammatory cytokine release from THP-1 cells. Collectively, pre-incinerated nanoclay displayed interaction with macrophage membrane components (molecular initiating event), increased pro-inflammatory mediators, and increased inflammatory cell recruitment (two key events) in the lung fibrosis adverse outcome pathway. [Description provided by NIOSH]
• Subjects:
  Air Pollutants, Occupational Aluminum Silicates Blood Cytotoxins Immune System Lung Lung Diseases Macrophages Occupational Health Particulate Matter Respiratory System Respiratory Tract Diseases Safety

  More +
• Keywords:
  Airborne Particulates Author Keywords: High-throughput Screening Coatings Cytokines Cytotoxic Effects Human Lung Cells Immune Reaction Incineration In Vitro Models In Vitro Study Lung Fibrosis Mouse Nanoclay Nanoclays Organic Coating Silicates

  More +
• ISSN:
  1743-8977
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  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
• Pages in Document:
  16
• Volume:
  21
• NIOSHTIC Number:
  nn:20069405
• Citation:
  Part Fibre Toxicol 2024 Mar; 21:16
• Contact Point Address:
  Todd A. Stueckle, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV, 26505, USA
• Email:
  tstueckle@cdc.gov
• Federal Fiscal Year:
  2024
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  Particle and Fibre Toxicology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:571bebcc5b69d4747cbe3275e712e3c959f4c3b70e083396e3b04ff479e75cb1ad1c7adf96e74bb3878e5d9a5d037a5ae0747629d5292404dc73c2cff75f04c6
• Download URL:
  https://stacks.cdc.gov/view/cdc/207888/cdc_207888_DS1.pdf
• File Type:
  [PDF - 4.94 MB ]