反义蛋白激酶 C-α和 p47phox 可减轻生物繁育型糖尿病大鼠巨噬细胞中 C 反应蛋白的促炎作用。
Antisense to protein kinase C-alpha and p47phox attenuates the pro-inflammatory effects of human C-reactive protein in macrophages of biobreeding diabetic rats.
机构信息
Laboratory for Atherosclerosis and Metabolic Research, Department of Pathology and Laboratory Medicine, University of California at Davis, Sacramento, CA 95817, USA.
出版信息
Diab Vasc Dis Res. 2012 Oct;9(4):315-9. doi: 10.1177/1479164112452165. Epub 2012 Jul 16.
OBJECTIVE
Type 1 diabetes mellitus (T1DM) is a pro-inflammatory state characterized by high C-reactive protein (CRP) levels. Previously, we showed that CRP accentuated a macrophage (MO) activity in spontaneously diabetic biobreeding (BB) rats and increased the MO activity of protein kinase C-alpha (PKC-α) and p47phox. In this report, we tested the effects of molecular inhibition of CRP effects on MO activity using antisense oligonucleotide (ASO) to both PKC-α and p47phox.
METHODS
Prior to administration of human C-reactive protein (hCRP) daily for 3 days, ASO or scrambled ASO to either PKC-α or p47phox was also delivered for 3 days and after killing on day 4, peritoneal MOs were isolated.
RESULTS
The increase in the levels of superoxide anion, interleukin (IL)-1, monocyte chemoattractant protein-1 (MCP-1), tumour necrosis factor-alpha (TNF-α) and IL-6 release in MOs with hCRP compared to human albumin was significantly attenuated by antisense to either PKC-α and p47phox (p < 0.01 vs. scrambled ASO; n = 5 per group).
CONCLUSION
Our novel data suggest that antisense to either PKC-α or p47phox attenuates the pro-inflammatory effects of human CRP on MOs in diabetic rats.
目的
1 型糖尿病（T1DM）是一种炎症状态，其特征是 C 反应蛋白（CRP）水平升高。此前，我们表明 CRP 加重了自发性糖尿病生物繁殖（BB）大鼠中巨噬细胞（MO）的活性，并增加了蛋白激酶 C-α（PKC-α）和 p47phox 的 MO 活性。在本报告中，我们使用针对 PKC-α 和 p47phox 的反义寡核苷酸（ASO）测试了抑制 CRP 作用对 MO 活性的影响。
方法
在每天给予人 C 反应蛋白（hCRP）3 天之前，还给予针对 PKC-α 或 p47phox 的 ASO 或乱序 ASO 3 天，并在第 4 天杀死后，分离腹腔 MO。
结果
与人白蛋白相比，hCRP 增加了 MO 中超氧阴离子、白细胞介素（IL）-1、单核细胞趋化蛋白-1（MCP-1）、肿瘤坏死因子-α（TNF-α）和 IL-6 的释放水平，抗 PKC-α 和 p47phox 的 ASO 明显减弱（与乱序 ASO 相比，p < 0.01；每组 n = 5）。
结论
我们的新数据表明，针对 PKC-α 或 p47phox 的 ASO 可减轻 CRP 对糖尿病大鼠 MO 中促炎作用。
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