Pulmonary fibrosis is an aberrant transformation of injured lung tissue. It is characterized by irreversible accumulation of extracellular matrix produced by fibroblasts and myofibroblasts during tissue remodeling, resulting in destruction and dysfunction of the lung. Asbestos is an important cause of pulmonary fibrosis. In response to asbestos exposure, alveolar macrophages and recruited monocytes generate reactive oxygen species (ROS), especially hydrogen peroxide (H2O2), pro-inflammatory cytokines, such as TNF-á and IL-1â, and induce subsequent collagen deposition in the lung. We have found that increased H2O2 levels are linked to the development of pulmonary fibrosis. Catalase converts H2O2 into water and oxygen, so we hypothesized that catalase may attenuate the development of pulmonary fibrosis.
Interestingly, previous studies from our lab have demonstrated that decreased H2O2 levels are associated not only with a decrease in fibrosis but also an increase in pro-inflammatory cytokines. In these current studies, we demonstrate that in the presence of asbestos, catalase increases TNF-á and IL-1â in macrophages while decreasing collagen production in fibroblasts. This is reversed when TNF-á receptor-1 is knocked down, suggesting that TNF-á may play a role in fibrosis development. To investigate these finding in vivo, catalase-treated mice showed decreased fibrosis histologically, decreased in collagen levels in BAL, and decreased hydroxyproline in lung tissue.
The major finding of my study is that catalase attenuates asbestos-induced fibrosis while increasing pro-inflammatory cytokines. This is contrary to the typical thought that pro-inflammatory states are associated with the fibrotic phenotype. The studies in this thesis may uncover a therapeutic target to attenuate the progression and/or development of pulmonary fibrosis.
| Identifer | oai:union.ndltd.org:uiowa.edu/oai:ir.uiowa.edu:etd-4761 |
| Date | 01 May 2013 |
| Creators | Shi, Lei |
| Contributors | Robertson, Larry W., 1947- |
| Publisher | University of Iowa |
| Source Sets | University of Iowa |
| Language | English |
| Detected Language | English |
| Type | thesis |
| Format | application/pdf |
| Source | Theses and Dissertations |
| Rights | Copyright 2013 Lei Shi |
Page generated in 0.001 seconds