Mediation of the single-walled carbon nanotubes induced pulmonary fibrogenic response by osteopontin and TGF-β1.

Autor: Khaliullin TO; a Department of Physiology & Pharmacology , West Virginia University , Morgantown , WV.; b Exposure Assessment Branch , NIOSH/CDC , Morgantown , WV., Kisin ER; b Exposure Assessment Branch , NIOSH/CDC , Morgantown , WV., Murray AR; b Exposure Assessment Branch , NIOSH/CDC , Morgantown , WV., Yanamala N; b Exposure Assessment Branch , NIOSH/CDC , Morgantown , WV., Shurin MR; c Department Pathology , University of Pittsburgh , Pittsburgh , PA., Gutkin DW; c Department Pathology , University of Pittsburgh , Pittsburgh , PA., Fatkhutdinova LM; d Department of Hygiene and Occupational Medicine , Kazan State Medical University , Kazan , Russia., Kagan VE; e Department of Pathology , University of Pittsburgh , Pittsburgh , PA., Shvedova AA; a Department of Physiology & Pharmacology , West Virginia University , Morgantown , WV.; b Exposure Assessment Branch , NIOSH/CDC , Morgantown , WV.
Jazyk: angličtina
Zdroj: Experimental lung research [Exp Lung Res] 2017 Oct; Vol. 43 (8), pp. 311-326.
DOI: 10.1080/01902148.2017.1377783
Abstrakt: Purpose of the Study: A number of in vivo studies have shown that pulmonary exposure to carbon nanotubes (CNTs) may lead to an acute local inflammatory response, pulmonary fibrosis, and granulomatous lesions. Among the factors that play direct roles in initiation and progression of fibrotic processes are epithelial-mesenchymal transition and myofibroblasts recruitment/differentiation, both mediated by transforming growth factor-β1 (TGF-β1). Yet, other contributors to TGF-β1 associated signaling, such as osteopontin (OPN) has not been fully investigated.
Materials and Methods: OPN-knockout female mice (OPN-KO) along with their wild-type (WT) counterparts were exposed to single-walled carbon nanotubes (SWCNT) (40 µg/mouse) via pharyngeal aspiration and fibrotic response was assessed 1, 7, and 28 days post-exposure. Simultaneously, RAW 264.7 and MLE-15 cells were treated with SWCNT (24 hours, 6 µg/cm 2 to 48 µg/cm 2 ) or bleomycin (0.1 µg/ml) in the presence of OPN-blocking antibody or isotype control, and TGF-β1 was measured in supernatants.
Results and Conclusions: Diminished lactate dehydrogenase activity at all time points, along with less pronounced neutrophil influx 24 h post-exposure, were measured in broncho-alveolar lavage (BAL) of OPN-KO mice compared to WT. Pro-inflammatory cytokine release (IL-6, TNF-α, MCP-1) was reduced. A significant two-fold increase of TGF-β1 was found in BAL of WT mice at 7 days, while TGF-β1 levels in OPN-KO animals remained unaltered. Histological examination revealed marked decrease in granuloma formation and less collagen deposition in the lungs of OPN-KO mice compared to WT. RAW 264.7 but not MLE-15 cells exposed to SWCNT and bleomycin had significantly less TGF-β1 released in the presence of OPN-blocking antibody. We believe that OPN is important in initiating the cellular mechanisms that produce an overall pathological response to SWCNT and it may act upstream of TGF-β1. Further investigation to understand the mechanistic details of such interactions is critical to predict outcomes of pulmonary exposure to CNT.
Databáze: MEDLINE
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