CCR5 plays an important role in resolving an inflammatory response to single-walled carbon nanotubes
Article first published online: 22 MAR 2012
Copyright © 2012 John Wiley & Sons, Ltd.
Journal of Applied Toxicology
Volume 33, Issue 8, pages 845–853, August 2013
How to Cite
Park, E.-J., Roh, J., Kim, S. N., Kim, Y., Han, S.-B. and Hong, J. T. (2013), CCR5 plays an important role in resolving an inflammatory response to single-walled carbon nanotubes. J. Appl. Toxicol., 33: 845–853. doi: 10.1002/jat.2744
- Issue published online: 21 JUN 2013
- Article first published online: 22 MAR 2012
- Manuscript Revised: 3 FEB 2012
- Manuscript Accepted: 3 FEB 2012
- Manuscript Received: 6 JAN 2012
Owing to the development of new materials and technology, the pollutants in the environment are becoming more varied and complex over time. In our previous study using ICR mice, we suggested that a single intratracheal instillation of single-walled carbon nanotubes (SWCNTs) induced early lung fibrosis and subchronic tissue damage. In the present study, to investigate the role of CCR5 in inflammatory responses to the uptake of SWCNTs, we compared BAL (Bronchoalveolar lavage) cell composition, cell cycles, cytokines, cell phenotypes, inflammatory response-related proteins, cell surface receptors and histopathology using CCR5 knockout (KO) and wild-type mice. Results showed that the distribution of neutrophils in BAL fluid significantly decreased in KO mice. The expression of apoptosis-related proteins including caspase-3, p53, phospho-p53, p21 and cleaved PARP, TGF βl and mesothelin markedly increased in KO mice compared with wild-type mice. Histopathological lesions were also more frequently noted in KO mice. Moreover, the secretion of IL-13 and IL-17 with IL-6 significantly increased in KO mice compared with wild-type mice, whereas that of IL-12 significantly decreased in comparison to wild-type mice. The distribution of B cells and CD8+ T cells was predominant in the inflammatory responses in KO mice, whereas that of T cells and CD4+ T cells was predominant in the inflammatory responses in wild-type mice. Furthermore, the expression of CCR4 and CCR7 significantly increased in KO mice. Based on these results, we suggest that the absence of CCR5 delays the resolution of inflammatory responses triggered by SWCNTs inflowing into the lungs and shifts inflammatory response for SWCNTs clearance from Th1-type to Th2-type. Copyright © 2012 John Wiley & Sons, Ltd.