Anti-oxidant inhibition of hyaluronan fragment-induced inflammatory gene expression.
Anti-oxidant inhibition of hyaluronan fragment-induced inflammatory gene expression.
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DOI：
10.1186/1476-9255-5-20
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发表时间：
2008-11-05
影响因子：
5.1
通讯作者：
Horton, Maureen R.
中科院分区：
文献类型：
--
作者：
Eberlein, Michael;Scheibner, Kara A.;Black, Katharine E.;Collins, Samuel L.;Chan-Li, Yee;Powell, Jonathan D.;Horton, Maureen R.
活性氧（ROS）和内源性抗氧化剂之间的平衡对于维持健康组织非常重要。过多的ROS状态发生在诸如ARDS和特发性肺纤维化的疾病中。氧化还原失衡将细胞外基质组分透明质酸（HA）分解成片段，所述片段激活先天性免疫应答并使组织损伤永久化。HA片段通过TLR和NF-κB途径诱导巨噬细胞和上皮细胞中的炎症基因表达。NAC和DMSO是有效的抗氧化剂，可以帮助平衡过量的ROS状态。本实验观察了H_2O_2、NAC和DMSO对HA片段诱导的肺泡巨噬细胞和上皮细胞炎症基因表达的影响。NAC和DMSO抑制HA片段诱导的肺泡和腹腔巨噬细胞TNF-α和KC蛋白的表达。NAC和DMSO还显示出对肺泡上皮细胞中IP-10蛋白表达的剂量依赖性抑制，但对IL-8蛋白没有抑制。此外，H2 O2与HA片段协同诱导炎性基因，其被NAC抑制。NAC和DMSO通过抑制NF-κB活化抑制HA诱导的基因表达，但NAC对HA片段AP-1介导的基因表达无影响。ROS在炎症的病理生理学“恶性循环”中起核心作用：组织损伤产生ROS，其使细胞外基质HA片段化，其又与ROS协同作用以激活先天免疫系统并进一步促进ROS、HA片段产生、炎症、组织损伤和最终纤维化。抗氧化剂NAC和DMSO通过抑制HA诱导的炎症基因表达，可以帮助重新平衡过多的ROS诱导的炎症。
The balance between reactive oxygen species (ROS) and endogenous anti-oxidants is important in maintaining healthy tissues. Excessive ROS states occur in diseases such as ARDS and Idiopathic Pulmonary Fibrosis. Redox imbalance breaks down the extracellular matrix component hyaluronan (HA) into fragments that activate innate immune responses and perpetuate tissue injury. HA fragments, via a TLR and NF-κB pathway, induce inflammatory gene expression in macrophages and epithelial cells. NAC and DMSO are potent anti-oxidants which may help balance excess ROS states. We evaluated the effect of H2O2, NAC and DMSO on HA fragment induced inflammatory gene expression in alveolar macrophages and epithelial cells. NAC and DMSO inhibit HA fragment-induced expression of TNF-α and KC protein in alveolar and peritoneal macrophages. NAC and DMSO also show a dose dependent inhibition of IP-10 protein expression, but not IL-8 protein, in alveolar epithelial cells. In addition, H2O2 synergizes with HA fragments to induce inflammatory genes, which are inhibited by NAC. Mechanistically, NAC and DMSO inhibit HA induced gene expression by inhibiting NF-κB activation, but NAC had no influence on HA-fragment-AP-1 mediated gene expression. ROS play a central role in a pathophysiologic "vicious cycle" of inflammation: tissue injury generates ROS, which fragment the extracellular matrix HA, which in turn synergize with ROS to activate the innate immune system and further promote ROS, HA fragment generation, inflammation, tissue injury and ultimately fibrosis. The anti-oxidants NAC and DMSO, by inhibiting the HA induced inflammatory gene expression, may help re-balance excessive ROS induced inflammation.
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影响因子：
3.1
作者：
KELLY, KA;HILL, MR;GIMBLE, JM
通讯作者：
GIMBLE, JM
影响因子：
27.4
作者：
LAURENT, TC;LAURENT, UBG;FRASER, JRE
通讯作者：
FRASER, JRE
影响因子：
5.8
作者：
Manoury B;Nenan S;Leclerc O;Guenon I;Boichot E;Planquois JM;Bertrand CP;Lagente V
通讯作者：
Lagente V
DOI：
10.1152/ajplung.2000.279.4.l707
发表时间：
2000-10-01
影响因子：
4.9
作者：
Horton, MR;Olman, MA;Lowenstein, CJ
通讯作者：
Lowenstein, CJ
DOI：
10.3109/17453679509157665
发表时间：
1995-10-01
期刊：
ACTA ORTHOPAEDICA SCANDINAVICA
影响因子：
--
作者：
Laurent, TC;Fraser, JRE;EngstromLaurent, A
通讯作者：
EngstromLaurent, A