Induction of type 3 deiodinase activity in inflammatory cells of mice with chronic local inflammation
Induction of type 3 deiodinase activity in inflammatory cells of mice with chronic local inflammation
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DOI：
10.1210/en.2005-0608
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发表时间：
2005-12-01
期刊：
影响因子：
4.8
通讯作者：
Visser, TJ
中科院分区：
文献类型：
--
作者：
Boelen, A;Kwakkel, J;Visser, TJ
在疾病期间，甲状腺激素代谢发生变化，即所谓的非甲状腺疾病（NTI）。NTI的特征是血清T-3下降，这是由于肝脏1型脱碘酶（D1）将T-4转化为T-3的甲状腺外转化减少，而血清TSH不增加。3型脱碘酶（D3）被认为在NTI过程中不起重要作用，但最近已经表明，D3活性在与缺氧相关的危重患者的肝脏和骨骼肌中上调。我们研究了D3基因的表达和活性在肝脏和肌肉/皮下组织的小鼠在疾病期间，这是由两种不同的刺激诱导：细菌内毒素（脂多糖）管理，导致急性全身反应，并在每个后肢turtenin注射，导致局部皮下脓肿。脂多糖诱导肝脏D1和D3活性迅速下降，但不影响后肢骨骼肌的活性。与此相反，局部炎症诱导的turerum没有降低肝脏D1和D3的活性，但显着增加D3的活性在肌肉/皮下组织样本包含脓肿，与强烈增加IL-1 β和IL-6 mRNA的表达。脓肿周围的炎性细胞显示D3和T-3转运蛋白单羧酸转运蛋白-8免疫反应性，而肌细胞未显示任何免疫反应性。总之，局部炎症强烈诱导D3活性的炎性细胞，特别是在入侵的多形核粒细胞，这表明增强局部降解的T-3。
During illness, changes in thyroid hormone metabolism occur, so-called nonthyroidal illness (NTI). NTI has been characterized by a fall of serum T-3 due to decreased extrathyroidal conversion of T-4 into T-3 by liver type 1 deiodinase (D1), without an increase in serum TSH. Type 3 deiodinase (D3) was thought not to play an important role during NTI, but recently it has been shown that D3 activity is up-regulated in liver and skeletal muscle of critically ill patients related to hypoxia. We studied D3 gene expression and activity in liver and muscle/subcutis of mice during illness, which was induced by two different stimuli: bacterial endotoxin (lipopolysaccharide) administration, resulting in an acute systemic response, and a turpentine injection in each hindlimb, resulting in a local sc abscess. Lipopolysaccharide induced a rapid decrease in liver D1 and D3 activity but not skeletal muscle of hindlimb. In contrast, local inflammation induced by turpentine did not decrease liver D1 and D3 activity but increased markedly D3 activity in the muscle/subcutis sample containing the abscess, associated with strongly increased IL-1 beta and IL-6 mRNA expression. Inflammatory cells, surrounding the abscess showed D3 and T-3-transporter monocarboxylate transporter-8 immunoreactivity, whereas muscle cells did not show any immunoreactivity. In conclusion, local inflammation strongly induces D3 activity in inflammatory cells, especially in invading polymorphonuclear granulocytes, suggesting enhanced local degradation of T-3.