TREM-1, HMGB1 and RAGE in the Shoulder Tendon: Dual Mechanisms for Inflammation Based on the Coincidence of Glenohumeral Arthritis.

TREM-1, HMGB1 and RAGE in the Shoulder Tendon: Dual Mechanisms for Inflammation Based on the Coincidence of Glenohumeral Arthritis.
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DOI:
10.1371/journal.pone.0165492
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发表时间:
2016
期刊:
影响因子:
3.7
通讯作者:
Agrawal DK
Agrawal DK
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Thankam FG;Dilisio MF;Dietz NE;Agrawal DK

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肩袖损伤(RCI)是成年人中一种主要的肌肉骨骼疾病,炎症和疼痛是主要的致病因素。其他临床情况如肩关节关节炎会加重炎症并延迟愈合反应。肌腱套关节炎症维持的机制和信号传导因素在很大程度上是未知的。本文旨在阐明炎症分子TREM-1(髓细胞上表达的触发受体-1)和危险相关分子模式(DAMPs),包括高迁移率组蛋白1 (HMGB-1)和RAGE(晚期糖基化终产物受体)在RCI中与盂肱关节炎严重程度的关系。收集肩关节肱二头肌肌腱(15份标本)和肩关节关节关节炎患者(1组,n = 4)和非肩关节关节关节炎患者(2组,n = 11) RCI手术后的血液(11份标本)用于研究。采用组织学、免疫荧光、RT-PCR和流式细胞术比较各组分子形态学变化。MRI和组织形态学评估显示1组患者严重炎症,而2组患者ECM紊乱明显,无任何炎症特征。观察到循环中性粒细胞和单核细胞中TREM-1表达显著增加。1组患者TREM-1、HMGB-1和RAGE水平升高以及CD68+和CD16+细胞证实了damp介导的炎症。在没有免疫细胞的情况下,组2患者的肌腱中TREM-1的表达出现了一个新的trem表达细胞群,通过实时PCR分析和免疫荧光证实了这一点。HMGB-1和RAGE在非肩关节关节炎患者肩部肱二头肌肌腱中的表达暗示trem -1介导的炎症不涉及免疫细胞,而在肩关节关节炎患者中,免疫细胞(主要是巨噬细胞)的浸润和激活释放介质诱导炎症。这可能是没有肩关节关节炎的患者没有典型炎症症状的ECM组织紊乱的原因。
Rotator cuff injury (RCI) is a major musculoskeletal disorder in the adult population where inflammation and pain are major contributing factors. Coincidence of other clinical conditions like glenohumeral arthritis aggravates inflammation and delays the healing response. The mechanism and signaling factors underlying the sustenance of inflammation in the rotator cuff joint are largely unknown. The present article aims to elucidate the involvement of inflammatory molecule, TREM-1 (Triggering Receptors Expressed on Myeloid cells-1), and danger-associated molecular patterns (DAMPs), including high mobility group protein 1 (HMGB-1) and RAGE (receptor for advanced glycation end products), in the setting of RCI with respect to the severity of glenohumeral arthritis. Biceps tendons (15 specimens) from the shoulder and blood (11 samples) from patients with glenohumeral arthritis (Group-1, n = 4) and without glenohumeral arthritis (Group-2, n = 11) after RCI surgery were obtained for the study. Molecular and morphological alterations between the groups were compared using histology, immunofluorescence, RT-PCR and flow cytometry. MRI and histomorphology assessment revealed severe inflammation in Group-1 patients while in Group-2 ECM disorganization was prominent without any hallmarks of inflammation. A significant increase in TREM-1 expression in circulating neutrophils and monocytes was observed. Elevated levels of TREM-1, HMGB-1 and RAGE in Group-1 patients along with CD68+ and CD16+ cells confirmed DAMP-mediated inflammation. Expression of TREM-1 in the tendon of Group-2 patients even in the absence of immune cells presented a new population of TREM-expressing cells that were confirmed by real-time PCR analysis and immunofluorescence. Expression of HMGB-1 and RAGE in the biceps tendon from the shoulder of patients without glenohumeral arthritis implied TREM-1-mediated inflammation without involving immune cells, whereas in patients with glenohumeral arthritis, infiltration and the activation of the immune cells, primarily macrophages, release mediators to induce inflammation. This could be the reason for ECM disorganization without the classical signs of inflammation in patients without glenohumeral arthritis.
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