Annexin A1 regulates intestinal mucosal injury, inflammation, and repair.
Annexin A1 regulates intestinal mucosal injury, inflammation, and repair.
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膜联蛋白A1调节肠粘膜损伤，炎症和修复。
DOI：
10.4049/jimmunol.181.7.5035
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发表时间：
2008-10-01
期刊：
影响因子：
--
通讯作者：
Nusrat A
中科院分区：
文献类型：
--
作者：
Babbin BA;Laukoetter MG;Nava P;Koch S;Lee WY;Capaldo CT;Peatman E;Severson EA;Flower RJ;Perretti M;Parkos CA;Nusrat A
在粘膜炎症过程中，一系列复杂的促炎和保护机制调节炎症和损伤的严重程度。抗炎介质的分泌是控制炎症反应和促进上皮恢复和屏障恢复的关键机制。AnxA 1是一种有效的抗炎蛋白，在炎症模型中发挥关键的免疫调节作用。虽然AnxA 1已被证明在炎症期间在肠粘膜组织中分泌，但其在调节损伤/炎症反应中的潜在作用尚不清楚。在这项研究中，我们证明，AnxA 1缺陷的动物表现出更大的临床发病率和组织病理学粘膜损伤葡聚糖硫酸钠（DSS）诱导的结肠炎的易感性增加。此外，与野生型（WT）对照小鼠相比，在AnxA 1（−/−）动物中观察到DSS给药停药后恢复受损，这与炎性细胞浸润无关。由于AnxA 1通过刺激ALX/FPRL-1发挥其抗炎特性，我们探讨了这种受体-配体相互作用在调节DSS诱导的结肠炎中的作用。有趣的是，用ALX/FPRL-1激动剂15-epi-lipoxin A4治疗逆转了AnxA 1（−/−）小鼠对DSS结肠炎的敏感性增强。相反，15-表脂环素A4没有显著改善WT动物的疾病严重程度。此外，ALX/FPLR-1在对照组和DSS处理的WT和AnxA 1缺陷动物中的差异表达表明，AnxA 1在病理生理条件下调节ALX/FPRL-1表达中具有潜在作用。总之，这些结果支持内源性AnxA 1在肠粘膜上皮的保护和修复特性中的作用。
During mucosal inflammation, a complex array of proinflammatory and protective mechanisms regulates inflammation and severity of injury. Secretion of anti-inflammatory mediators is a mechanism that is critical in controlling inflammatory responses and promoting epithelial restitution and barrier recovery. AnxA1 is a potent anti-inflammatory protein that has been implicated to play a critical immune regulatory role in models of inflammation. Although AnxA1 has been shown to be secreted in intestinal mucosal tissues during inflammation, its potential role in modulating the injury/inflammatory response is not understood. In this study, we demonstrate that AnxA1-deficient animals exhibit increased susceptibility to dextran sulfate sodium (DSS)-induced colitis with greater clinical morbidity and histopathologic mucosal injury. Furthermore, impaired recovery following withdrawal of DSS administration was observed in AnxA1 (−/−) animals compared with wild-type (WT) control mice that was independent of inflammatory cell infiltration. Since AnxA1 exerts its anti-inflammatory properties through stimulation of ALX/FPRL-1, we explored the role of this receptor-ligand interaction in regulating DSS-induced colitis. Interestingly, treatment with an ALX/FPRL-1 agonist, 15-epi-lipoxin A4 reversed the enhanced sensitivity of AnxA1 (−/−) mice to DSS colitis. In contrast, 15-epilipoxin A4 did not significantly improve the severity of disease in WT animals. Additionally, differential expression of ALX/FPLR-1 in control and DSS-treated WT and AnxA1-deficient animals suggested a potential role for AnxA1 in regulating ALX/FPRL-1 expression under pathophysiological conditions. Together, these results support a role of endogenous AnxA1 in the protective and reparative properties of the intestinal mucosal epithelium.
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DOI：
10.1016/j.plefa.2005.05.008
发表时间：
2005-09-01
影响因子：
3
作者：
Gavins, FNE;Sawmynaden, P;Perretti, M
通讯作者：
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影响因子：
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Hardt, WD
影响因子：
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