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Tribbles homolog 3 (TRB3) downregulates endotoxin-induced NO production in murine macrophages

Kim, Jaemi; Baik, Eun Joo; Lee, Soo Hwan
Department of Physiology, Ajou University School of Medicine
The expression of inducible nitric oxide synthase (iNOS) and the production of nitric oxide (NO) are modulated by a variety of factors. 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. Thus, in order to explore the possible role of TRB3 in glucose enhancing effect, we investigated the effects of TRB3 on the expression of iNOS and the production of NO in Raw264.7 cells stimulated with bacterial lipopolysaccharide(LPS). The expression level of TRB3 significantly increased in Raw264.7 cells exposed to low glucose (5 mM). When cells were exposed to low glucose, the levels of iNOS expression and NO production were significantly reduced compared to high glucose. Overexpression of TRB3 attenuated LPS-induced iNOS expression and NO production. Furthemore, the knock-down of endogenous TRB3 using siRNA upregulated the iNOS expression and NO production. These results indicate that TRB3 can downregulate endotoxin-induced iNOS expression and NO production in murine macrophages.
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