Antioxidant treatment attenuates cytokine and chemokine levels in murine macrophages following silica exposure

Alveolar macrophages play a key role in the development of silicosis by rel easing a host of mediators, such as, cytokines and chemokines, which contri bute to a complex network of interactions that result in the onset of lung injury, inflammation, and potentially fibrosis. Using a murine macrophage c ell line, RAW 264.7, we exposed the cells to cristobalite-silica (35 mu g/c m(2)) in the presence or absence of antioxidants and various modifiers of c ellular antioxidant status. Treatment with dimethyl sulfoxide, extracellula r glutathione, or N-acetyl-L-cysteine (NAC) decreased cristobalite-induced tumor necrosis factor (TNF)-alpha mRNA levels by 40%, 20%, and 42%, respect ively. TNF-alpha protein levels were decreased by 90%, 32%, and 53%, respec tively. Cristobalite-induced macrophage inflammatory protein (MIP)-2 mRNA l evels were reduced by 52%, 38%, and 57%, with DMSO, GSH, and NAC treatment, respectively. Both MIP-1 alpha and MIP-1 beta mRNA levels were reduced at a magnitude similar to the reduction in TNF-alpha mRNA levels, whereas mono cyte chemotactic protein (MCP)-1 mRNA levels were reduced at a magnitude si milar to the reduction in MIP-2 mRNA levels following antioxidant treatment . These results suggests that the macrophage response to cristobalite expos ure is mediated at least in part by oxidant stress. (C) 1999 Academic Press .