Effects of nitric oxide on notexin-induced muscle inflammatory responses.
Effects of nitric oxide on notexin-induced muscle inflammatory responses.
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DOI：
10.7150/ijbs.10283
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发表时间：
2015
影响因子：
9.2
通讯作者：
Liao H
中科院分区：
文献类型：
--
作者：
Liu X;Wu G;Shi D;Zhu R;Zeng H;Cao B;Huang M;Liao H
过度的炎症反应可能会延迟肌肉损伤后的再生并损伤正常的肌纤维。重要的是能够减弱炎症反应并减少炎性细胞浸润，以改善肌肉再生形成，从而导致肌损伤后更好的肌肉功能恢复。本研究采用Notexin诱导的小鼠骨骼肌损伤模型，探讨一氧化氮（NO）在骨骼肌炎症过程中的作用。肌内注射Notexin（胫前肌，TA）制备小鼠肌损伤。NO合酶抑制剂（L-NAME）或NO供体（SNP）腹腔注射。在损伤后第4天和第7天，通过qRT-PCR和Western Blot评估肌肉组织中肌肉自身抗原和toll样受体（TLR）的表达;单核细胞/巨噬细胞的肌内浸润（CD 11b+或F4/80+细胞），CD 8 + T细胞（CD 3 ε+ CD 8 α+），凋亡细胞免疫荧光法检测受损肌肉中表达MHC-Ⅰ类分子H-2Kb的肌纤维（CD 11b + caspase 3+）;通过qRT-PCR评估了与肌肉损伤诱导的炎症反应期间优先生物学作用相关的细胞因子和趋化因子的mRNA表达。我们检测到与未处理相比，用SNP处理的受损肌肉中单核细胞/巨噬细胞浸润减少，凋亡细胞增加。同样，SNP处理下调受损肌肉中肌肉自身抗原TLR 3的mRNA和蛋白水平，以及TNF-α、IL-6、MCP-1、MCP-3和MIP-1α的mRNA水平。相反，L-NAME诱导更严重的炎性细胞浸润肌内，上述炎症介质的mRNA水平升高。值得注意的是，在L-NAME治疗后第7天，我们观察到受损肌肉中MHC-I（H2-Kb）阳性新肌纤维和浸润的CD 8 + T细胞的数量增加。本文的结果表明，NO可以作为内源性抗炎分子在进行性肌肉炎症过程中起作用。我们的发现可能为优化基于NO的治疗方法以改善肌损伤后的肌肉再生提供新的见解。
Excessive inflammatory response may delay the regeneration and damage the normal muscle fibers upon myoinjury. It would be important to be able to attenuate the inflammatory response and decrease inflammatory cells infiltration in order to improve muscle regeneration formation, resulting in better muscle functional recovery after myoinjury. This study was undertaken to explore the role of Nitric oxide (NO) during skeletal muscle inflammatory process, using a mouse model of Notexin induced myoinjury. Intramuscular injection (tibialis anterior, TA) of Notexin was performed for preparing mice myoinjury. NO synthase inhibitor (L-NAME) or NO donor (SNP) was intraperitoneally injected into model mice. On day 4 and 7 post-injury, expression of muscle-autoantigens and toll-like receptors (TLRs) was evaluated from muscle tissue by qRT-PCR and Western Blot; the intramuscular infiltration of monocytes/macrophage (CD11b+ or F4/80+ cells), CD8+ T cell (CD3ε+CD8α+), apoptotic cell (CD11b+caspase3+), and MHC-I molecule H-2Kb-expressing myofibers in damaged muscle were assessed by imunoflourecence analysis; the mRNAs expression of cytokines and chemokines associated with the preferential biological role during the muscle damage-induced inflammation response, were assessed by qRT-PCR. We detected the reduced monocytes/macrophages infiltration, and increased apoptotic cells in the damaged muscle treated with SNP comparing to untreatment. As well, SNP treatment down-regulated mRNA and protein levels of muscle autoantigens, TLR3, and mRNA levels of TNF-α, IL-6, MCP-1, MCP-3, and MIP-1α in damaged muscle. On the contrary, L-NAME induced more severe intramuscular infiltration of inflammatory cells, and mRNA level elevation of the above inflammatory mediators. Notably, we observed an increased number of MHC-I (H2-Kb) positive new myofibers, and of the infiltrated CD8+ T cells in damaged muscle at the day 7 after L-NAME treatment. The result herein shows that, NO can act as an endogenous anti-inflammatory molecule during the ongoing muscle inflammation. Our finding may provide new insight to optimize NO-based therapies for improving muscle regeneration after myoinjury.
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DOI：
10.1073/pnas.93.17.9142
发表时间：
1996-08-20
影响因子：
11.1
作者：
Chang, WJ;Iannaccone, ST;Stull, JT
通讯作者：
Stull, JT
影响因子：
2
作者：
Tatsumi, R.;Hattori, A.;Ito, T.
通讯作者：
Ito, T.
影响因子：
15.9
作者：
Rubinstein, I;Abassi, Z;Better, OS
通讯作者：
Better, OS
影响因子：
5.2
作者：
Buono, Roberta;Vantaggiato, Chiara;Pisa, Viviana;Azzoni, Emanuele;Bassi, Maria Teresa;Brunelli, Silvia;Sciorati, Clara;Clementi, Emilio
通讯作者：
Clementi, Emilio
影响因子：
4.4
作者：
Rigamonti, Elena;Touvier, Thierry;Rovere-Querini, Patrizia
通讯作者：
Rovere-Querini, Patrizia