title: The sources of inflammatory mediators in the lung after silica exposure.
abstract: The expression of 10 genes implicated in regulation of the inflammatory processes in the lung was studied after exposure of alveolar macrophages (AMs) to silica in vitro or in vivo. Exposure of AMs to silica in vitro up-regulated the messenger RNA (mRNA) levels of three genes [interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein-2 (MIP-2)] without a concomitant increase in the protein levels. AMs isolated after intratracheal instillation of silica up-regulated mRNA levels of four additional genes [granulocyte/macrophage-colony stimulating factor (GM-CSF), IL-1beta, IL-10, and inducible nitric oxide synthase]. IL-6, MCP-1, and MIP-2 protein levels were elevated in bronchoalveolar lavage fluid. Fibroblasts under basal culture conditions express much higher levels of IL-6 and GM-CSF compared with AMs. Coculture of AMs and alveolar type II cells, or coculture of AMs and lung fibroblasts, in contact cultures or Transwell chambers, revealed no synergistic effect. Therefore, such interaction does not explain the effects seen in vivo. Identification of the intercellular communication in vivo is still unresolved. However, fibroblasts appear to be an important source of inflammatory mediators in the lung.
authors.affiliation: Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia, USA. mir8@cdc.gov
authors.forename: K Murali Krishna
authors.initials: KM
authors.lastname: Rao
authors.forename: Dale W
authors.initials: DW
authors.lastname: Porter
authors.forename: Terence
authors.initials: T
authors.lastname: Meighan
authors.forename: Vince
authors.initials: V
authors.lastname: Castranova
mesh_terms: D000818:Animals; D016207:Cytokines / Q000096:biosynthesis*; D005347:Fibroblasts / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects*; D007249:Inflammation / Q000503:physiopathology*; D008168:Lung / Q000276:immunology* / Q000473:pathology*; D016676:Macrophages, Alveolar; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012822:Silicon Dioxide / Q000633:toxicity*; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D012822:Silicon Dioxide