Effect of fiber length on carbon nanotube-induced fibrogenesis.
Given their extremely small size and light weight, carbon nanotubes (CNTs) can be readily inhaled by human lungs resulting in increased rates of pulmonary disorders, particularly fibrosis. Although the fibrogenic potential of CNTs is well established, there is a lack of consensus regarding the contribution of physicochemical attributes of CNTs on the underlying fibrotic outcome. We designed an experimentally validated in vitro fibroblast culture model aimed at investigating the effect of fiber length on single-walled CNT (SWCNT)-induced pulmonary fibrosis. The fibrogenic response to short and long SWCNTs was assessed via oxidative stress generation, collagen expression and transforming growth factor-beta (TGF-β) production as potential fibrosis biomarkers. Long SWCNTs were significantly more potent than short SWCNTs in terms of reactive oxygen species (ROS) response, collagen production and TGF-β release. Furthermore, our finding on the length-dependent in vitro fibrogenic response was validated by the in vivo lung fibrosis outcome, thus supporting the predictive value of the in vitro model. Our results also demonstrated the key role of ROS in SWCNT-induced collagen expression and TGF-β activation, indicating the potential mechanisms of length-dependent SWCNT-induced fibrosis. Together, our study provides new evidence for the role of fiber length in SWCNT-induced lung fibrosis and offers a rapid cell-based assay for fibrogenicity testing of nanomaterials with the ability to predict pulmonary fibrogenic response in vivo.
Department of Pharmaceutical Sciences, West Virginia University, 1, Medical Center Drive, Morgantown, WV 26506, USA. amanke1@mix.wvu.edu.
Amruta
A
Manke
Department of Pharmaceutical Sciences, West Virginia University, 1, Medical Center Drive, Morgantown, WV 26506, USA. sluanpitpong@hsc.wvu.edu.
Sudjit
S
Luanpitpong
Department of Chemical Engineering, Statler College of Engineering and Mineral Resources, West Virginia University, 395 Evansdale Drive, PO Box 6102, Morgantown, WV 26506, USA. cerasela-zoica.dinu@mail.wvu.edu.
Chenbo
C
Dong
Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, 1095 Willowdale Rd., Morgantown, WV 26505, USA. lmw6@cdc.gov.
Liying
L
Wang
Department of Pharmaceutical Sciences, West Virginia University, 1, Medical Center Drive, Morgantown, WV 26506, USA. xiaoqinghe6@gmail.com.
Xiaoqing
X
He
Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, 1095 Willowdale Rd., Morgantown, WV 26505, USA. lob0@cdc.gov.
Lori
L
Battelli
Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, 1095 Willowdale Rd., Morgantown, WV 26505, USA. rhd8@cdc.gov.
Raymond
R
Derk
Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, 1095 Willowdale Rd., Morgantown, WV 26505, USA. sst2@cdc.gov.
Todd A
TA
Stueckle
Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, 1095 Willowdale Rd., Morgantown, WV 26505, USA. dhp7@cdc.gov.
Dale W
DW
Porter
Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, 1095 Willowdale Rd., Morgantown, WV 26505, USA. sst2@cdc.gov.
Tina
T
Sager
Department of Mechanical and Aerospace Engineering, Statler College of Engineering and Mineral Resources, West Virginia University, 395 Evansdale Drive, PO Box 6102, Morgantown, WV 26506, USA. honglei.gou@mail.wvu.edu.
Honglei
H
Gou
Department of Chemical Engineering, Statler College of Engineering and Mineral Resources, West Virginia University, 395 Evansdale Drive, PO Box 6102, Morgantown, WV 26506, USA. cerasela-zoica.dinu@mail.wvu.edu.
Cerasela Zoica
CZ
Dinu
Department of Mechanical and Aerospace Engineering, Statler College of Engineering and Mineral Resources, West Virginia University, 395 Evansdale Drive, PO Box 6102, Morgantown, WV 26506, USA. nick.wu@mail.wvu.edu.
Nianqiang
N
Wu
Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, 1095 Willowdale Rd., Morgantown, WV 26505, USA. rpm7@cdc.gov.
Robert R
RR
Mercer
Department of Pharmaceutical Sciences, West Virginia University, 1, Medical Center Drive, Morgantown, WV 26506, USA. yrojan@hsc.wvu.edu.
Yon
Y
Rojanasakul
D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D003603:Cytotoxins / Q000737:chemistry / Q000633:toxicity; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D037742:Nanotubes, Carbon / Q000737:chemistry* / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
D024042:Collagen Type I; D003603:Cytotoxins; D037742:Nanotubes, Carbon; D017382:Reactive Oxygen Species; D016212:Transforming Growth Factor beta