Multi-walled carbon nanotube (MWCNT)-induced fibrogenic signaling in a human lung epithelial-fibroblast co-culture system

Details

• Personal Author:
  Mihalchik AL ; Qian Y ; Sisler JD
• Description:
  It has been established that MWCNT induce pulmonary fibrosis in in vivo models. In vitro studies of fibroblasts in monoculture have also investigated MWCNT toxicity. However, the role of other cell types and cellular communication in the mechanisms of MWCNT-induced fibrosis needs further study. Our lab previously elucidated inflammatory and vascular effects of MWCNT exposure in an epithelial-endothelial co-culture model; here, we employ a system to examine fibrogenic responses to MWCNT. In this study, we assessed the effects of pristine MWCNT at an occupationally relevant dose on fibroblasts grown in a transwell co-culture system of apical Beas-2B human bronchial epithelial cells and basolateral WI-38 normal human lung fibroblasts. To address the impact of cell-to-cell communication between the epithelium and underlying fibroblasts on pulmonary fibrosis, we first measured chemokine (C-C motif) ligand 2 (CCL2) concentrations by ELISA in monoculture and co-culture conditioned media. CCL2 levels were significantly elevated in the basolateral chamber of MWCNT-exposed cells in co-culture, without similar changes in WI-38 monoculture or unexposed WI-38 grown in the co-culture system. CCL2 has been shown to be increased and upregulated in patients with idiopathic pulmonary fibrosis, usual interstitial pneumonia, and bronchiolitis obliterans syndrome, and responsible for fibroblast production of TGF-beta and procollagen. In further support, MWCNT-exposed WI-38 in co-culture exhibit increased collagen type I, a hallmark of fibrosis, as compared to unexposed WI-38 in co-culture. These results suggest that the epithelial-fibroblast co-culture system may be more reflective of the fibrotic disease state instead of monoculture systems, and may allow us to further elucidate the mechanism of MWCNT-induced fibrosis in vitro. [Description provided by NIOSH]
• Subjects:
  Cells, Cultured Enzymes Fibrosis Laboratories Lung Lung Diseases Occupational Health Respiratory System Respiratory Tract Diseases Safety Toxicology

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• Keywords:
  Cell Cultures Cell Culture Techniques Cell Signaling Cell Type Cellular Reactions ELISA Endothelial Cells Enzyme-linked Immunosorbent Assay Exposure Assessment Fibroblasts Fibrogenicity Gene Regulation Humans Laboratory Techniques Laboratory Testing Lung Cells Lung Fibrosis Models Multi-walled Carbon Nanotubes MWCNT Nanotechnology

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Louisiana ; OSHA Region 3 ; OSHA Region 6 ; 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:
  150
• Issue:
  1
• NIOSHTIC Number:
  nn:20047822
• Citation:
  Toxicologist 2016 Mar; 150(1):585
• CAS Registry Number:
  Carbon nanotubes (CAS RN 308068-56-6)
• Federal Fiscal Year:
  2016
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 55th Annual Meeting and ToxExpo, March 13-17, 2016, New Orleans, Louisiana
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:227adfd806563bb4762e129de49c50c2ff92f4700d3273ee04973902149efcc07e5a6a7d0409457451d6a075eebed21987c33c5efb6e5e2e64880a86798e472a
• Download URL:
  https://stacks.cdc.gov/view/cdc/202790/cdc_202790_DS1.pdf
• File Type:
  [PDF - 441.85 KB ]