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Intratracheal instillation of diesel particles upregulates messages for several genes involved in inflammation, in the first 24 hours.
Rao-KMK; Ma-JY; Meighan-T; Barger-MK; Pack-DK; Vallyathan-VK
FASEB J 2004 Mar; 18(5)(Suppl):A1138
Diesel particles at 3 concentrations (1, 7, and 10 mg/200 g body weight) were instilled into rats intratracheally. Rats were sacrificed at 1, 7, and 30 days to study the effects on gene expression in rat alveolar macrophages (AM) obtained by bronchoalveolar lavage and lung tissue (LT). The mRNA levels of the genes were measured by real-time RT/PCR. Seven genes (IL-1ƒÒ, IL-10, iNOS, MCP-1, MIP-2, TGF-ƒÒ1, and TNF-ƒÑ) were measured in AM and three genes in LT (ICAM-1, GM-CSF, and RANTES). At day 1, diesel particles at the highest dose induced significant upregulation of IL-1ƒÒ, IL-10, iNOS, MCP-1 and MIP-2. In contrast, there was a significant downregulation of TGF-ƒÒ1 and no change in TNF-ƒÑ mRNA levels. There was no change in the mRNA levels of RANTES, ICAM-1 and GM-CSF in LT. Consistent with the mRNA levels seen in AM, there was an increase in nitric oxide production, MCP-1 and MIP-2 protein levels in supernatants of AM obtained at day 1 and cultured for an additional 24 h. These observations indicate that diesel particles produce rapid upregulation in AM of messages of several genes involved in evoking an inflammatory response. The main changes seem to be confined to AM rather than lung tissue. These insights should prove useful in designing strategies to reduce the pathological effects caused by diesel exposure.
Animal-studies; Diesel-emissions; Particle-aerodynamics; Lung; Pulmonary-disorders; Pulmonary-function; Genes; Genetic-factors
Issue of Publication
The FASEB Journal
Page last reviewed: March 11, 2019
Content source: National Institute for Occupational Safety and Health Education and Information Division