Kwakkel J, van Beeren H C, Ackermans M T, Platvoet-Ter Schiphorst M C, Fliers E, Wiersinga W M, Boelen A
Department of Endocrinology and Metabolism Laboratory of Endocrinology, Department of Clinical Chemistry, Academic Medical Center, University of Amsterdam, F5-165, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
J Endocrinol. 2009 Nov;203(2):263-70. doi: 10.1677/JOE-09-0118. Epub 2009 Aug 5.
We have previously shown that skeletal muscle deiodinase type 2 (D2) mRNA (listed as Dio2 in MGI Database) is upregulated in an animal model of acute illness. However, human studies on the expression of muscle D2 during illness report conflicting data. Therefore, we evaluated the expression of skeletal muscle D2 and D2-regulating factors in two mouse models of illness that differ in timing and severity of illness: 1) turpentine-induced inflammation, and 2) Streptococcus pneumoniae infection. During turpentine-induced inflammation, D2 mRNA and activity increased compared to pair-fed controls, most prominently at day 1 and 2, whereas after S. pneumoniae infection D2 mRNA decreased. We evaluated the association of D2 expression with serum thyroid hormones, (de-)ubiquitinating enzymes ubiquitin-specific peptidase 33 and WD repeat and SOCS box-containing 1 (Wsb1), cytokine expression and activation of inflammatory pathways and cAMP pathway. During chronic inflammation the increased muscle D2 expression is associated with the activation of the cAMP pathway. The normalization of D2 5 days after turpentine injection coincides with increased Wsb1 and tumor necrosis factor alpha expression. Muscle interleukin-1beta (Il1b) expression correlated with decreased D2 mRNA expression after S. pneumoniae infection. In conclusion, muscle D2 expression is differentially regulated during illness, probably related to differences in the inflammatory response and type of pathology. D2 mRNA and activity increases in skeletal muscle during the acute phase of chronic inflammation compared to pair-fed controls probably due to activation of the cAMP pathway. In contrast, muscle D2 mRNA decreases 48 h after a severe bacterial infection, which is associated with local Il1b mRNA expression and might also be due to diminished food-intake.
我们之前已经表明，骨骼肌2型脱碘酶（D2）mRNA（在MGI数据库中列为Dio2）在急性疾病动物模型中上调。然而，关于疾病期间肌肉D2表达的人体研究报告的数据相互矛盾。因此，我们在两种疾病时间和严重程度不同的小鼠疾病模型中评估了骨骼肌D2及其调节因子的表达：1）松节油诱导的炎症，以及2）肺炎链球菌感染。在松节油诱导的炎症期间，与配对喂食的对照组相比，D2 mRNA和活性增加，在第1天和第2天最为明显，而在肺炎链球菌感染后D2 mRNA下降。我们评估了D2表达与血清甲状腺激素、（去）泛素化酶泛素特异性肽酶33和含WD重复序列及SOCS盒的1（Wsb1）、细胞因子表达以及炎症途径和cAMP途径激活之间的关联。在慢性炎症期间，肌肉D2表达的增加与cAMP途径的激活有关。松节油注射5天后D2的正常化与Wsb1和肿瘤坏死因子α表达的增加相一致。肺炎链球菌感染后，肌肉白细胞介素-1β（Il1b）表达与D2 mRNA表达降低相关。总之，疾病期间肌肉D2表达受到不同调节，这可能与炎症反应和病理类型的差异有关。与配对喂食的对照组相比，在慢性炎症急性期，骨骼肌中D2 mRNA和活性增加，这可能是由于cAMP途径的激活。相比之下，严重细菌感染48小时后肌肉D2 mRNA下降，这与局部Il1b mRNA表达有关，也可能是由于食物摄入减少所致。
