The synthetic peroxisome proliferator-activated receptor-γ agonist ciglitazone attenuates neuroinflammation and accelerates encapsulation in bacterial brain abscesses
The synthetic peroxisome proliferator-activated receptor-γ agonist ciglitazone attenuates neuroinflammation and accelerates encapsulation in bacterial brain abscesses
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DOI：
10.4049/jimmunol.180.7.5004
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发表时间：
2008-04-01
影响因子：
4.4
通讯作者：
Esen, Nilufer
中科院分区：
文献类型：
--
作者：
Kielian, Tammy;Syed, Mohsin Md.;Esen, Nilufer
脑脓肿由化脓性实质感染引起，通常由革兰氏阳性菌如金黄色葡萄球菌引起。虽然感染后引起的宿主免疫应答对于有效的细菌遏制是必不可少的，但这种应答也有助于通过坏死导致脑实质的显著损失，这可以通过调节炎症应答来减少。当感染后3天开始治疗时，评价了格列酮（一种具有抗炎特性的PPAR-gamma激动剂）影响脑脓肿发展过程的能力。有趣的是，在给予环格列酮后，与细菌相关的细菌负荷显著降低，这可以部分地解释为环格列酮增强了S。小胶质细胞的金黄色葡萄球菌吞噬作用。此外，环格列酮减弱了脑脓肿发展过程中选择的炎症介质的表达，包括诱导型NO合酶、TNF-α、IL-1 β、CXCL 2和CCL 3。出乎意料的是，环格列酮也加速了脑脓肿的包裹，其典型表现为纤维连接蛋白和α-平滑肌肌动蛋白阳性肌成纤维细胞的表达增加。总的来说，通过其减轻过度炎症和加速脓肿包裹的能力，环格列酮可以有效地隔离脑脓肿并限制细菌传播。
Brain abscesses result from a pyogenic parenchymal infection commonly initiated by Gram-positive bacteria such as Staphylococcus aureus. Although the host immune response elicited following infection is essential for effective bacterial containment, this response also contributes to the significant loss of brain parenchyma by necrosis that may be reduced by modulating the inflammatory response. Ciglitazone, a PPAR-gamma agonist with anti-inflammatory properties, was evaluated for its ability to influence the course of brain abscess development when treatment was initiated 3 days following infection. Interestingly, abscess-associated bacterial burdens were significantly lower following ciglitazone administration, which could be explained, in part, by the finding that ciglitazone enhanced S. aureus phagocytosis by microglia. In addition, ciglitazone attenuated the expression of select inflammatory mediators during brain abscess development including inducible NO synthase, TNF-alpha, IL-1 beta,CXCL2, and CCL3. Unexpectedly, ciglitazone also accelerated brain abscess encapsulation, which was typified by the heightened expression of fibronectin and a-smooth muscle actin-positive myofibroblasts. Collectively, through its ability to attenuate excessive inflammation and accelerate abscess encapsulation, ciglitazone may effectively sequester brain abscesses and limit bacterial dissemination.