The Sources of Inflammatory Mediators in the Lung after Silica Exposure K. Murali Krishna Rao, Dale W. Porter, Terence Meighan, and Vince Castranova Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia, USA 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-1ß, 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. Key words: alveolar macrophages, alveolar type II cells, cytokines, fibroblasts, gene expression, lung, silica. Environ Health Perspect 112: 1679-1685 (2004) . doi:10.1289/ehp.7295 available via http://dx.doi.org/ [Online 16 August 2004] Address correspondence to K.M.K. Rao, Box 2015, PPRB/HELD/NIOSH, 1095 Willowdale Road, Morgantown, WV 26505 USA. Telephone: (304) 285-6169. Fax: (304) 285-5938. E-mail: mir8@cdc.gov The authors declare they have no competing financial interests. Received 28 May 2004 ; accepted 16 August 2004. The full version of this article is available for free in HTML or PDF formats. |