S100A9 induced inflammatory responses are mediated by distinct damage associated molecular patterns (DAMP) receptors in vitro and in vivo.
S100A9 induced inflammatory responses are mediated by distinct damage associated molecular patterns (DAMP) receptors in vitro and in vivo.
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DOI：
10.1371/journal.pone.0115828
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Sims GP
中科院分区：
文献类型：
--
作者：
Chen B;Miller AL;Rebelatto M;Brewah Y;Rowe DC;Clarke L;Czapiga M;Rosenthal K;Imamichi T;Chen Y;Chang CS;Chowdhury PS;Naiman B;Wang Y;Yang D;Humbles AA;Herbst R;Sims GP
内源性损伤相关分子模式（DAMP）（包括S100家族成员）的释放与感染、细胞应激、组织损伤和癌症相关。该钙结合蛋白家族，特别是S100 A8、S100 A9和S100 A12的细胞外功能正在被描述。它们似乎通过晚期糖基化终产物（DAMP）或TLR 4受体介导其功能，但这些DAMP及其模式识别受体的相对生理作用仍存在相当大的不确定性。在这项研究中，我们调查了S100蛋白诱导促炎细胞因子和细胞迁移的能力，以及在体外介导这些反应的TLR 4的贡献。使用腺病毒递送鼠S100 A9，我们还检查了S100 A9同源二聚体在体内触发肺部炎症的潜力。S100 A8、S100 A9和S100 A12，而不是S100 A8/A9异二聚体，诱导了适度水平的TLR 4介导的来自人PBMC的细胞因子产生。相反，对于大多数S100，包括S100 A9，TLR 4阻断抑制S100介导的THP 1细胞和主要白细胞群的细胞迁移，而TLR 4阻断没有影响。鼻内给药小鼠S100 A9腺病毒诱导特异性的、时间依赖性的主要是巨噬细胞浸润，这与BAL液中升高的S100 A9水平和促炎细胞因子相一致。炎性细胞因子在TLR 4缺陷型小鼠中显著消除，但出乎意料的是，TLR 4信号传导的丧失或RAGE缺陷并没有明显影响S100 A9介导的肺病理学或肺泡腔中的炎性细胞浸润。这些数据表明，生理水平的S100 A9同源二聚体可以在体内触发炎症反应，尽管在体外阻断IL-10和TLR 4能够抑制反应，但该反应主要不依赖于这两种受体。
Release of endogenous damage associated molecular patterns (DAMPs), including members of the S100 family, are associated with infection, cellular stress, tissue damage and cancer. The extracellular functions of this family of calcium binding proteins, particularly S100A8, S100A9 and S100A12, are being delineated. They appear to mediate their functions via receptor for advanced glycation endproducts (RAGE) or TLR4, but there remains considerable uncertainty over the relative physiological roles of these DAMPs and their pattern recognition receptors. In this study, we surveyed the capacity of S100 proteins to induce proinflammatory cytokines and cell migration, and the contribution RAGE and TLR4 to mediate these responses in vitro. Using adenoviral delivery of murine S100A9, we also examined the potential for S100A9 homodimers to trigger lung inflammation in vivo. S100A8, S100A9 and S100A12, but not the S100A8/A9 heterodimer, induced modest levels of TLR4-mediated cytokine production from human PBMC. In contrast, for most S100s including S100A9, RAGE blockade inhibited S100-mediated cell migration of THP1 cells and major leukocyte populations, whereas TLR4-blockade had no effect. Intranasal administration of murine S100A9 adenovirus induced a specific, time-dependent predominately macrophage infiltration that coincided with elevated S100A9 levels and proinflammatory cytokines in the BAL fluid. Inflammatory cytokines were markedly ablated in the TLR4-defective mice, but unexpectedly the loss of TLR4 signaling or RAGE-deficiency did not appreciably impact the S100A9-mediated lung pathology or the inflammatory cell infiltrate in the alveolar space. These data demonstrate that physiological levels of S100A9 homodimers can trigger an inflammatory response in vivo, and despite the capacity of RAGE and TLR4 blockade to inhibit responses in vitro, the response is predominately independent of both these receptors.
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影响因子：
5.1
作者：
Bargagli, E.;Olivieri, C.;Rottoli, P.
通讯作者：
Rottoli, P.
影响因子：
9.3
作者：
Ehlermann, Philipp;Eggers, Kai;Remppis, Andrew
通讯作者：
Remppis, Andrew
影响因子：
4.8
作者：
Leclerc, Estelle;Fritz, Gunter;Galichet, Arnaud
通讯作者：
Galichet, Arnaud
影响因子：
5.9
作者：
Lee, Tae-Hyeong;Jang, An-Soo;Park, Choon-Sik
通讯作者：
Park, Choon-Sik
DOI：
10.1084/jem.20080132
发表时间：
2008-09-29
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Cheng P;Corzo CA;Luetteke N;Yu B;Nagaraj S;Bui MM;Ortiz M;Nacken W;Sorg C;Vogl T;Roth J;Gabrilovich DI
通讯作者：
Gabrilovich DI