Froy Oren, Hananel Amit, Chapnik Nava, Madar Zecharia
Institute of Biochemistry, Food Science and Nutrition, Faculty of Agricultural, Food and Environmental Quality, The Hebrew University of Jerusalem, PO Box 12, Rehovot 76100, Israel.
Mol Immunol. 2007 Feb;44(5):796-802. doi: 10.1016/j.molimm.2006.04.009. Epub 2006 Jun 5.
Many infections are associated with diabetes, as the ability of the body to fight pathogens is impaired. Recently, altered levels of defensins and polymorphism in Toll-like receptors (TLRs), two crucial components of the innate immune system, have been associated with diabetes. To study the functionality of the innate immune system during diabetes, we measured the expression levels of rat beta-defensin 1 (rBD-1), rBD-2, rTLR2, and rTLR4 in the kidney, lung, liver, and brain of streptozotocin-induced diabetic rats with and without insulin treatment. In the kidneys of diabetic rats, lower levels of rBD-1, rTLR2, and rTLR4 were found. These low levels could be restored with insulin treatment. In contrast, rBD-2 was highly induced in the lungs of diabetic rats, most likely, as a result of a pro-inflammatory response. In the liver and brain of diabetic rats, lower levels of TLRs and/or defensins could not be restored with insulin treatment. Our findings suggest for the first time that high blood glucose and/or insulin deficiency abrogates the expression level of the innate immune system components, defensins and TLRs, explaining the recurrent infections during diabetes. These findings may lay the grounds for future design of novel treatments that will induce defensins and TLRs and, as a result, bolster the immune system in diabetic patients.
许多感染都与糖尿病相关，因为身体对抗病原体的能力受损。最近，作为先天性免疫系统的两个关键组成部分，防御素水平的改变和Toll样受体（TLR）的多态性与糖尿病有关。为了研究糖尿病期间先天性免疫系统的功能，我们测量了链脲佐菌素诱导的糖尿病大鼠在有或没有胰岛素治疗的情况下，肾脏、肺、肝脏和大脑中大鼠β-防御素1（rBD-1）、rBD-2、rTLR2和rTLR4的表达水平。在糖尿病大鼠的肾脏中，发现rBD-1、rTLR2和rTLR4的水平较低。这些低水平可以通过胰岛素治疗恢复。相比之下，rBD-2在糖尿病大鼠的肺中高度诱导，最有可能是促炎反应的结果。在糖尿病大鼠的肝脏和大脑中，TLR和/或防御素的低水平不能通过胰岛素治疗恢复。我们的研究结果首次表明，高血糖和/或胰岛素缺乏会消除先天性免疫系统成分防御素和TLR的表达水平，这解释了糖尿病期间的反复感染。这些发现可能为未来设计新的治疗方法奠定基础，这些方法将诱导防御素和TLR，从而增强糖尿病患者的免疫系统。
