Interleukin expression after injury and the effects of interleukin-1 receptor antagonist.
Interleukin expression after injury and the effects of interleukin-1 receptor antagonist.
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DOI：
10.1371/journal.pone.0071631
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Vanderby R
中科院分区：
文献类型：
--
作者：
Chamberlain CS;Leiferman EM;Frisch KE;Brickson SL;Murphy WL;Baer GS;Vanderby R
韧带愈合遵循一系列复杂的协调事件，涉及各种细胞类型、细胞因子以及其他因素，产生比天然组织更像瘢痕的机械性劣质组织。巨噬细胞提供细胞因子的持续来源以调节炎性细胞粘附和迁移以及成纤维细胞增殖。研究巨噬细胞活化和血管生成高峰期韧带愈合所固有的白细胞介素可能阐明随后瘢痕形成中涉及的炎症介质。在此，我们使用了一种大鼠愈合模型，在手术切断其内侧副韧带（MCL）后进行分析。在损伤后第3天和第7天，收集韧带并用于微阵列分析。在12种显著修饰的白细胞介素中，白细胞介素-1家族的组分显著上调。因此，我们研究了白细胞介素-1受体拮抗剂（IL-1 Ra）对MCL愈合的影响。横断大鼠MCL在手术时接受PBS或IL-1 Ra。抑制IL-1活化可降低促炎细胞因子（IL-1α、IL-1β、IL-12、IL-2和IFN-γ）、肌成纤维细胞和增殖细胞，并增加抗炎细胞因子（IL-10）、内皮细胞/血管腔、M2巨噬细胞和肉芽组织大小，而不影响机械性能。这些结果支持IL-1 Ra调节MCL局部肉芽组织成分和细胞因子产生以产生炎症较小的瞬时环境的概念。总的来说，IL-1 Ra可能通过刺激M2巨噬细胞和改变肉芽组织成分在愈合级联反应的早期具有治疗潜力。然而，本研究中使用的单剂量IL-1 Ra不足以维持更再生的早期反应。由于对大多数测试的愈合成分的短暂影响，IL-1 Ra可能具有更大的持续递送治疗潜力。
Ligament healing follows a series of complex coordinated events involving various cell types, cytokines, as well as other factors, producing a mechanically inferior tissue more scar-like than native tissue. Macrophages provide an ongoing source of cytokines to modulate inflammatory cell adhesion and migration as well as fibroblast proliferation. Studying interleukins inherent to ligament healing during peak macrophage activation and angiogenesis may elucidate inflammatory mediators involved in subsequent scar formation. Herein, we used a rat healing model assayed after surgical transection of their medial collateral ligaments (MCLs). On days 3 and 7 post-injury, ligaments were collected and used for microarray analysis. Of the 12 significantly modified interleukins, components of the interleukin-1 family were significantly up-regulated. We therefore examined the influence of interleukin-1 receptor antagonist (IL-1Ra) on MCL healing. Transected rat MCLs received PBS or IL-1Ra at the time of surgery. Inhibition of IL-1 activation decreased pro-inflammatory cytokines (IL-1α, IL-1β, IL-12, IL-2, and IFN-γ), myofibroblasts, and proliferating cells, as well as increased anti-inflammatory cytokines (IL-10), endothelial cells/blood vessel lumen, M2 macrophages, and granulation tissue size without compromising the mechanical properties. These results support the concept that IL-1Ra modulates MCL-localized granulation tissue components and cytokine production to create a transient environment that is less inflammatory. Overall, IL-1Ra may have therapeutic potential early in the healing cascade by stimulating the M2 macrophages and altering the granulation tissue components. However, the single dose of IL-1Ra used in this study was insufficient to maintain the more regenerative early response. Due to the transient influence on most of the healing components tested, IL-1Ra may have greater therapeutic potential with sustained delivery.
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影响因子：
3.7
作者：
Hanke ML;Angle A;Kielian T
通讯作者：
Kielian T
影响因子：
2.8
作者：
Chamberlain, Connie S.;Crowley, Erin M.;Kobayashi, Hirohito;Eliceiri, Kevin W.;Vanderby, Ray
通讯作者：
Vanderby, Ray
影响因子：
--
作者：
Nigrovic, Peter A.;Mannion, Melissa;Higgins, Gloria C.
通讯作者：
Higgins, Gloria C.
影响因子：
4
作者：
FONTANA, A;HENGARTNER, H;COHEN, G
通讯作者：
COHEN, G
影响因子：
5.5
作者：
Nixon, R.;Bansback, N.;Brennan, A.
通讯作者：
Brennan, A.