Inflammation and rapid-onset fibrosis in mouse lungs induced by multi-walled carbon nanotubes.
Dong-J; Porter-DW; Battelli-L; Wolfarth-MG; Richardson-D; Ma-Q
Fibrosis: From Bench to Bedside, Proceedings of the Keystone Symposia on Molecular and Cellular Biology, March 23-28, 2014, Keystone, Colorado. Silverthorne, CO: Keystone Symposia, 2014 Mar; :96
The production of multi-walled carbon nanotubes (MWCNT) has been significantly increased in recent decades due to their widespread applications, which has led to a concern regarding their impacts on human health because of the similarities of MWCNT to asbestos fibers. Recently, pulmonary fibrosis was associated with the major effects of MWCNT on health, but with limited progress in understanding the extent of MWCNT exposure in initiation and progression of lung fibrosis and in identifying the molecules that contribute to this pathologic consequence. Here, we showed MWCNT were a potent fibrotic agent that induced rapid-onset fibrosis upon single exposure to low doses 7 days post-exposure in C57BL/6 mice, indicated by histological analysis and increased expression of fibrosis marker genes, such as aSMA and Col1a1 . The MWCNT exposure elicited significant inflammatory response evidenced by inflammatory infiltration in the lungs and markedly increased PMN count and lactate dehydrogenase activity in the BAL from fibrotic lungs. To understand the underlying mechanism, we determined the expression of several groups of molecules including the genes involved in inflammatory immune responses, extracellular matrix remodeling and cytotoxicity, by PCR array analysis. Elevated gene expression was verified in the lungs and in fibrotic foci, which occurred mainly in the regions where MWCNT were distributed, including proinflammatory cytokines and matrix remodeling enzymes. Molecular mechanism studies were performed in alveolar macrophages and lung fibroblasts to understand the relation between inflammation and fibrosis under MWCNT exposure, and the signaling pathways involved in both processes. Results from this study will contribute to both general concept on fibrogenesis and mechanism identification specific to MWCNT-initiated fibrosis.
Nanotechnology; Pulmonary-disorders; Pulmonary-system-disorders; Respiratory-system-disorders; Fibrogenesis; Fibrogenicity; Fibrosis; Laboratory-animals; Animal-studies; Animals
Fibrosis: From Bench to Bedside, Proceedings of the Keystone Symposia on Molecular and Cellular Biology, March 23-28, 2014, Keystone, Colorado