title: Overexpression of apolipoprotein A1 in the lung abrogates fibrosis in experimental silicosis.
abstract: The inhalation of silica particles induces silicosis, an inflammatory and fibrotic lung disease characterized by the early accumulation of macrophages and neutrophils in the airspace and subsequent appearance of silicotic nodules as a result of progressive fibrosis. This study evaluated whether apolipoprotein A1 (ApoA1) protects against ongoing fibrosis and promotes the resolution of established experimental lung silicosis. Crystallized silica was intratracheally administered to 6- to 8-week-old transgenic mice expressing human ApoA1 in their alveolar epithelial cells (day 0). ApoA1 was overexpressed beginning on day 7 (ApoA1_D7 group) or day 15 (ApoA1_D15 group). The mice were sacrificed on day 30 for an evaluation of lung histology; the measurement of collagen, transforming growth factor-b1 and lipoxin A4; and a TUNEL assay for apoptotic cells. The ApoA1_D7 and D15 groups showed significant reductions in the silica-induced increase in inflammatory cells, silicotic nodule area, and collagen deposition compared with the silica-treated ApoA1 non-overexpressing mice. The level of transforming growth factor-b1 decreased in the bronchoalveolar lavage fluid, whereas lipoxin A4 was increased in the ApoA1_D7 and D15 groups compared with the silica-treated ApoA1 non-overexpressing mice. The silica-induced increase in the number of apoptotic cells was significantly reduced in the lungs of mice overexpressing ApoA1. Overexpression of ApoA1 decreased silica-induced lung inflammation and fibrotic nodule formation. The restoration of lipoxin A4 may contribute to the protective effect of ApoA1 overexpression against silica-induced lung fibrosis.
authors: Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Gyeonggi-Do, South Korea.
authors: Eun hee
authors: Eh
authors: Lee
authors: Eun-ju
authors: EJ
authors: Lee
authors: Hee jeong
authors: Hj
authors: Kim
authors: An soo
authors: As
authors: Jang
authors: Eun suk
authors: Es
authors: Koh
authors: Soo-taek
authors: ST
authors: Uh
authors: Yong hoon
authors: Yh
authors: Kim
authors: Sung-woo
authors: SW
authors: Park
authors: Choon-sik
authors: CS
authors: Park
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000235:genetics*; D017209:Apoptosis; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D004318:Doxycycline / Q000494:pharmacology; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D011658:Pulmonary Fibrosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012822:Silicon Dioxide / Q000009:adverse effects; D012829:Silicosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003074:Solitary Pulmonary Nodule / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D016632:Apolipoprotein A-I; D018836:Inflammation Mediators; D053773:Transforming Growth Factor beta1; D012822:Silicon Dioxide; D003094:Collagen; D004318:Doxycycline