Department of Disease Control and Prevention, Fujita Health University Graduate School of Health Sciences, Toyoake, 470-1192, Japan.
School of Bioscience and Biotechnology, Tokyo University of Technology, Hachioji, 192-0982, Japan.
Sci Rep. 2018 Oct 29;8(1):15917. doi: 10.1038/s41598-018-34166-4.
Indoleamine 2,3-dioxygenase 2 (Ido2) is a recently identified catalytic enzyme in the tryptophan-kynurenine pathway that is expressed primarily in monocytes and dendritic cells. To elucidate the biological role of Ido2 in immune function, we introduced lipopolysaccharide (LPS) endotoxin shock to Ido2 knockout (Ido2 KO) mice, which led to higher mortality than that in the wild type (WT) mice. LPS-treated Ido2 KO mice had increased production of inflammatory cytokines (including interleukin-6; IL-6) in serum and signal transducer and activator of transcription 3 (stat3) phosphorylation in the spleen. Moreover, the peritoneal macrophages of LPS-treated Ido2 KO mice produced more cytokines than did the WT mice. By contrast, the overexpression of Ido2 in the murine macrophage cell line (RAW) suppressed cytokine production and decreased stat3 expression. Finally, RAW cells overexpressing Ido2 did not alter nuclear factor κB (NF-κB) or stat1 expression, but IL-6 and stat3 expression decreased relative to the control cell line. These results reveal that Ido2 modulates IL-6/stat3 signalling and is induced by LPS, providing novel options for the treatment of immune disorders.
吲哚胺 2,3-双加氧酶 2（Ido2）是色氨酸-犬尿氨酸途径中最近发现的一种催化酶，主要在单核细胞和树突状细胞中表达。为了阐明 Ido2 在免疫功能中的生物学作用，我们对 Ido2 敲除（Ido2 KO）小鼠进行了脂多糖（LPS）内毒素休克处理，结果发现其死亡率高于野生型（WT）小鼠。LPS 处理的 Ido2 KO 小鼠的血清中促炎细胞因子（包括白细胞介素 6；IL-6）和信号转导和转录激活因子 3（stat3）磷酸化水平增加。此外，LPS 处理的 Ido2 KO 小鼠的腹腔巨噬细胞产生的细胞因子多于 WT 小鼠。相比之下，IDO2 在小鼠巨噬细胞系（RAW）中的过表达抑制了细胞因子的产生，并降低了 stat3 的表达。最后，过表达 Ido2 的 RAW 细胞不会改变核因子 κB（NF-κB）或 stat1 的表达，但与对照细胞系相比，IL-6 和 stat3 的表达下降。这些结果表明，IDO2 调节 IL-6/stat3 信号转导，并被 LPS 诱导，为治疗免疫紊乱提供了新的选择。
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