PMID- 15579413 OWN - NLM STAT- MEDLINE DCOM- 20050302 LR - 20181113 IS - 0091-6765 (Print) IS - 1552-9924 (Electronic) IS - 0091-6765 (Linking) VI - 112 IP - 17 DP - 2004 Dec TI - The sources of inflammatory mediators in the lung after silica exposure. PG - 1679-86 AB - 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. FAU - Rao, K Murali Krishna AU - Rao KM AD - Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia, USA. mir8@cdc.gov FAU - Porter, Dale W AU - Porter DW FAU - Meighan, Terence AU - Meighan T FAU - Castranova, Vince AU - Castranova V LA - eng PT - Journal Article PL - United States TA - Environ Health Perspect JT - Environmental health perspectives JID - 0330411 RN - 0 (Cytokines) RN - 0 (RNA, Messenger) RN - 7631-86-9 (Silicon Dioxide) SB - IM MH - Animals MH - Cytokines/*biosynthesis MH - Fibroblasts/physiology MH - Gene Expression Regulation/*drug effects MH - Inflammation/*physiopathology MH - Lung/*immunology/*pathology MH - Macrophages, Alveolar MH - RNA, Messenger/biosynthesis MH - Rats MH - Rats, Sprague-Dawley MH - Silicon Dioxide/*toxicity MH - Up-Regulation PMC - PMC1253659 EDAT- 2004/12/08 09:00 MHDA- 2005/03/03 09:00 PMCR- 2004/12/01 CRDT- 2004/12/08 09:00 PHST- 2004/12/08 09:00 [pubmed] PHST- 2005/03/03 09:00 [medline] PHST- 2004/12/08 09:00 [entrez] PHST- 2004/12/01 00:00 [pmc-release] AID - ehp0112-001679 [pii] AID - 10.1289/ehp.7295 [doi] PST - ppublish SO - Environ Health Perspect. 2004 Dec;112(17):1679-86. doi: 10.1289/ehp.7295.