Tiazofurin modulates lipopolysaccharide-activated microglia in vitro

Abstract

Tiazofurin is a purine nucleoside analogue, with a broad spectrum of antitumoral and anti-inflammatory properties. In the present study, we have investigated the effect of tiazofurin on microglial inflammatory response to lipopolysaccharide in vitro. The cytotoxic effect of the drug was examined by sulforhodamine B assay. The Griess method was used to quantify nitrite production. Microglial morphology was assessed by measuring cell body size. Release of the pro-inflammatory cytokines, tumor necrosis factor-?, interleukin-1?, interleukin-6, and the anti-inflammatory cytokine interleukin- 10, were evaluated by enzyme-linked immunosorbent assay. Our data showed that tiazofurin decreased the number of activated microglia, lowered nitric oxide production and reduced the average cell surface of these cells. Tiazofurin reduced tumor necrosis factor-?, interleukin-6 and increased interleukin-10 secretion. Conversely, this drug promoted the release of interleukin-1?. Results obtained in this study indicate that TR displayed both anti- and pro-inflammatory modulation of activated microglia that could be relevant for its antitumor action within the central nervous system.