| Summary: | 碩士 === 高雄醫學大學 === 公共衛生學研究所碩士班 === 94 === 英文摘要
High levels of ambient respirable pollutants have been linked to the increased risk of chronic lung diseases, including asthma and chronic obstructive pulmonary disease. Our previous study demonstrated that acute exposure to ufCB cause acute lung injury. It has recently been shown that HGF might exhibit a potent function for resolution of bleomycin induced lung injuries.
The aim of this study was to explore the role of HGF in ufCB induced acute and subacute lung injury.
Animal ICR mice, aged 5 wks and weighted 25-28 gm. Particle ufCB, 14 nm in diameter. Animal were intratracheal instilled with 100 μg of ufCB very other day. Quantitations of total proteins and HGF and differential analysis of leukocytes were performed. ROS production was determined using 2’, 7’-dichlorofluorescein diacetate (DCFH-DA). The level of c-Met expression was determined using Western blot analysis. Primary antibody against bromodeoxyuridine (BrdUrd) was used to detect the levels of DNA synthesis and cell proliferation.
A single exposure to ufCB significantly increased total proteins and inflammatory cells in BAL fluid. In conjunction, HGF in BAL was increased and maintained at significantly high level even 96 hr after exposure, compared to PBS control. The level of HGF in THP-1 (cultured macrophages) reached the maximal level at 72 hr after exposure to 100 μg ufCB. The increase of HGF in THP-1 after 6-hr exposure to ufCB could be reversed by antioxidant (SOD) treatment. Likewise, the increase of HGF in A549 by a 6-hr exposure to ufCB was reversed by SOD. However, a 6-hr or longer exposure to ufCB did not induce HGF production in cultured fibroblasts. Cultured fibroblasts increased HGF production in response to TNF-α challenge.
In subacute model with ufCB exposure every other day, neutrophil and lymphocyte infiltrations, the production of total proteins and HGF were significantly increased in BAL fluid after each exposure. Repeated exposure four times to ufCB increased the epithelial cell proliferations in bronchioles, compared to the control group. More BrdUrd-positive stainings were found in the epithelial layers of bronchioles and type II cells of alveoli. The expression of HGF receptor (c-Met) was highly elevated in lung after first exposure. Then, the levels of c-Met were not significantly altered after repeated exposure, when compared with PBS control.
Our data suggest that the induction of HGF after exposure to ufCB is cell-specific. Most intriguing, HGF could reduce the oxidative stress level incurred by ufCB exposure. Therefore, in acute exposure to ufCB, HGF could increase cell survival by reducing ROS production and increase cell proliferation to facilitate tissue repair. Subacute exposures to ufCB could also increase the production of HGF and the proliferation of lung epithelial cells. This may cause lung tissue remodeling.
Key Words: ultrafine carbon black, Heptocyte growth factor, BrdUrd, cell proliferation, tissue remodeling.
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