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Departments of 1 Environmental Medicine and 2 Pediatrics, University of Rochester School of Medicine, Rochester, New York 14642
Recent evidence has suggested that epithelial
cells may contribute to the inflammatory response in the lung after
exposure to crystalline silica through the production of and response
to specific growth factors, chemokines, and cytokines. However, the exact cellular and molecular responses of epithelial cells to silica
exposure remains unclear. Using a murine alveolar type II cell line [murine lung epithelial (MLE)-15 cell line],
we measured the early changes in various cytokine and chemokine mRNA
species after exposure of the cells to 4-35
µg/cm2 of silica (cristobalite),
interferon (IFN)-
, tumor necrosis factor (TNF)-
, and
lipopolysaccharide (LPS) alone or in combination. Total mRNA was
isolated and assayed with an RNase protection assay after 6 and 24 h of
exposure. Cristobalite exposure alone led to an increase in monocyte
chemotactic protein (MCP)-1, macrophage inflammatory protein (MIP)-2,
and regulated on activation normal T cells expressed and secreted
(RANTES) mRNAs. Treatment with IFN-
alone increased MCP-1 mRNA
levels. Treatment with TNF-
or LPS alone led to an increase in MCP-1
and MIP-2 mRNA. The combination of cristobalite plus TNF-
led to an
additive increase in MCP-1 and MIP-2, whereas cristobalite plus IFN-
or LPS had a synergistic effect. We also found with a
TNF-
-neutralizing antibody that TNF-
plays a major role in
mediating the type II cell chemokine response to cristobalite exposure.
The results indicate that the cristobalite-induced chemokine response
in the lung epithelium is mediated in part by TNF-
and can be
enhanced by macrophage- and lymphocyte-derived inflammatory mediators
in an additive and synergistic fashion.
airway epithelium; interferon-
; lipopolysaccharide; monocyte
chemotactic protein-1; macrophage inflammatory protein-2; regulated on
activation normal T cells expressed and secreted; tumor necrosis
factor-
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