Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing, China; Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL, USA.
Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL, USA.
Clin Immunol. 2018 Oct;195:139-148. doi: 10.1016/j.clim.2018.06.003. Epub 2018 Jun 9.
The major metabolic feature of diabetes is hyperglycemia which has been linked to the diabetes inflammatory processes, and diabetes-related vulnerability to infection. In the present study, we assessed how glucose affected PBMCs in type I interferon (IFN) production and subsequent signaling. We found that the moderately elevated glucose promoted, and high glucose suppressed type I IFN production, respectively. Pre-exposure to high glucose rendered monocytes more sensitive to IFN-α stimulation with heightened signaling, whereas, instantaneous addition of high glucose did not exhibit such effect. Consistent with this finding, the mRNA levels of IFN-α-induced IRF-7 in PBMCs were positively correlated with HbA1c levels of diabetes patients. Additionally, we found that high glucose promoted the production of other proinflammatory cytokines/chemokines. This study suggests that hyperglycemia may affect the inflammatory process in diabetes via promoting proinflammatory cytokines, as well as the host defense against microbial infections through impeding type I IFN production and signaling.
糖尿病的主要代谢特征是高血糖，高血糖与糖尿病炎症过程和糖尿病易感染有关。在本研究中，我们评估了葡萄糖如何影响 I 型干扰素 (IFN) 的产生以及随后的信号转导。我们发现，中度升高的葡萄糖分别促进和抑制 I 型 IFN 的产生。高葡萄糖预先暴露使单核细胞对 IFN-α刺激更敏感，信号增强，而瞬时添加高葡萄糖则没有这种作用。与这一发现一致的是，PBMCs 中 IFN-α诱导的 IRF-7 的 mRNA 水平与糖尿病患者的 HbA1c 水平呈正相关。此外，我们发现高葡萄糖促进了其他促炎细胞因子/趋化因子的产生。这项研究表明，高血糖可能通过促进促炎细胞因子，以及通过阻碍 I 型 IFN 的产生和信号转导来影响糖尿病中的炎症过程，从而影响宿主对微生物感染的防御。
