Tribbles homolog 3 (TRB3) downregulates endotoxin-induced NO production and NF-kB activation in murine macrophages.
Kim, Jaemi; Baik, Eun Joo; Lee, Soo Hwan
Department of Physiology
Tribbles homolog 3 (TRB3), a human homolog of Drosophila tribble, has been found to interact with a variety of signaling molecules to regulate cellular functions. Recently, it was shown that TRB3 inhibited MCP-1 expression in podocytes, suggesting its role in the regulation of inflammation. Moreover, the expression of TRB3 is reported to be induced by lack of nutrients. Previously, we have shown that endotoxin-induced iNOS expression was enhanced under high glucose condition. In this study, we investigated the effects of TRB3 on LPS-induced iNOS expression in Raw264.7 cells to explore the possible role of TRB3 in glucose enhancing effect. The expression level of TRB3 significantly increased in Raw264.7 cells exposed to low glucose (5 mM). On the other hand, high glucose (25 mM) enhanced LPS-induced iNOS expression and NO production and upregulated NF-kB activity in a reporter assay. Ectopic expression of TRB3 attenuated LPS-induced iNOS expression, NO production and transcriptional activity of NF-kB, whereas the knock-down of endogenous TRB3 using siRNA upregulated these responses. These results suggest that TRB3 might downregulate endotoxin-induced iNOS expression and NO production through attenuation of NF-kB activity, providing insight into glucose-enhancing effect on LPS-induced iNOS expression in murine macrophages.
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