Characterization of RAGE, HMGB1, and S100β in Inflammation-Induced Preterm Birth and Fetal Tissue Injury
Characterization of RAGE, HMGB1, and S100β in Inflammation-Induced Preterm Birth and Fetal Tissue Injury
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DOI：
10.2353/ajpath.2009.090156
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发表时间：
2009-09-01
影响因子：
6
通讯作者：
Buhimschi, Irina A.
中科院分区：
文献类型：
--
作者：
Buhimschi, Catalin S.;Baumbusch, Margaret A.;Buhimschi, Irina A.
免疫激活代表了由有害的外源性（微生物）和内源性[高迁移率族蛋白-1（HMGB 1），S100钙结合蛋白]炎症诱导剂触发的适应性反应。细胞应激或坏死导致HMGB 1和S100蛋白在细胞外区室中释放，在细胞外区室中，它们通过与晚期糖基化终产物（AGEs）受体结合而作为损伤相关的分子模式分子（或警报素）。虽然损伤相关的分子模式分子在组织损伤部位的积累决定了胎盘的生物学，但胎盘在介导产前胎儿损伤中的作用仍然未知。首先，我们研究了出生时人类胎儿炎症的强度与S100（一种内源性β受体拮抗剂）、HMGB 1和S100 β蛋白之间的关系。我们发现，在人类胎儿中，炎症反应明显较低。RMGB 1水平与胎儿循环中的白细胞介素-6和S100 β水平显著相关。然后，我们评估了E16小鼠胎儿特定器官中HMGB 1和S100 β的组织表达水平和区域。使用内毒素诱导的胎儿损伤和早产的动物模型，我们确定炎症在组织损伤部位诱导了β-淀粉样蛋白和HMGB 1表达的显著变化，但不是S100 β。我们的研究结果表明，在炎症诱导的早产的胎儿交付的细胞损伤的重要介质中，HMGB 1可能是。(Am病理学杂志2009，175：958-975; DOI. 10.2353/ajpath.2009.090156）
Immune activation represents an adaptive reaction triggered by both noxious exogenous (microbes) and endogenous [high mobility group box-1 protein (HMGB1), S100 calcium binding proteins] inducers of inflammation. Cell stress or necrosis lead the release of HMGB1 and S100 proteins in the extracellular compartment where they act as damage-associated molecular pattern molecules (or alarmins) by engaging the receptor for advanced glycation end-products (RAGE). Although the biology of RAGE is dictated by the accumulation of damage-associated molecular pattern molecules at sites of tissue injury, the role of RAGE in mediating antenatal fetal injury remains unknown. First, we studied the relationships at birth between the intensity of human fetal inflammation and sRAGE (an endogenous RAGE antagonist), HMGB1, and S100 beta protein. We found significantly lower sRAGE in human fetuses that mounted robust inflammatory responses. RMGB1 levels correlated significantly with levels of interleukin-6 and S100 beta in fetal circulation. We then evaluated the levels and areas of tissue expression of RAGE, HMGB1, and S100 beta in specific organs of mouse fetuses on E16. Using an animal model of endotoxin-induced fetal damage and preterm birth, we determined that inflammation induces a significant change in expression of RAGE and HMGB1, but not S100 beta, at sites of tissue damage. Our findings indicate that RAGE and HMGB1 may be important mediators of cellular injury in fetuses delivered in the setting of inflammation-induced preterm birth. (Am J Pathol 2009,175:958-975; DOI. 10.2353/ajpath.2009.090156)