Hyaluronic acid oligosaccharides suppress TLR3-dependent cytokine expression in a TLR4-dependent manner.
Hyaluronic acid oligosaccharides suppress TLR3-dependent cytokine expression in a TLR4-dependent manner.
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DOI：
10.1371/journal.pone.0072421
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Gallo RL
中科院分区：
文献类型：
--
作者：
Kim MY;Muto J;Gallo RL
已经提出损伤后从皮肤释放内源性分子影响炎症。最近的研究发现，促炎信号可以由受损的内源性自身RNA产生，并且该事件由TLR 3检测。相反，已经提出在损伤后释放透明质酸（HA）的内源性片段以抑制由TLR 4驱动的LPS诱导的炎症。在这项研究中，我们研究了HA寡聚体是否也可以影响TLR 3介导的炎症。将HA的四聚体形式（寡聚HA）加入MH-S细胞（小鼠肺泡巨噬细胞系）中，然后用poly（I：C）活化。ELISA分析表明，oligo-HA的存在抑制了poly（I：C）诱导的IL-6和TNFα的释放。通过定量RT-PCR测量，IL-6 mRNA表达也被抑制。为了确定oligo-HA抑制poly（I：C）的作用机制，用oligo-HA和poly（I：C）处理来自野生型（WT）、Tlr 2 −/−或Tlr 4 −/−小鼠的巨噬细胞。与WT细胞相似，寡聚HA抑制Tlr 2 −/−巨噬细胞，并保持对细胞因子释放的抑制。相反，Tlr 4 −/−巨噬细胞失去了被oligo-HA抑制的能力。寡聚HA处理WT后观察到Traf 1（TLR负调节因子）mRNA增加，但在Tlr 4 −/−巨噬细胞中未观察到，寡聚HA未抑制Traf 1 −/−巨噬细胞中的细胞因子反应性。这些结果表明，寡聚HA通过TLR 4和TRAF 1抑制TLR 3依赖性炎症。这一观察结果说明了损伤后释放的内源性产物的复杂免疫调节作用。
The release of endogenous molecules from the skin after injury has been proposed to influence inflammation. Recent studies have found that pro-inflammatory signals can be generated by damaged endogenous self-RNA, and this event is detected by TLR3. Conversely, release of endogenous fragments of hyaluronic acid (HA) after injury has been proposed to inhibit LPS induced inflammation driven by TLR4. In this study we investigated if HA oligomers could also influence inflammation mediated by TLR3. A tetramer form of HA (oligo-HA) was added to MH-S cells (mouse alveolar macrophage cell line) that were then activated by poly(I:C). ELISA analysis of culture supernatants showed that the presence of oligo-HA suppressed the poly(I:C) induced release of IL-6 and TNFα. IL-6 mRNA expression was also suppressed as measured by quantitative RT-PCR. To determine the mechanism of action for oligo-HA to inhibit poly(I:C), macrophages derived from wild-type (WT), Tlr2−/− or Tlr4−/− mice were treated with oligo-HA and poly(I:C). Similar to WT cells, Tlr2−/− macrophages were inhibited by oligo-HA and retained suppression of cytokine release. In contrast, Tlr4−/− macrophages lost the capacity to be suppressed by oligo-HA. An increase in Traf1 (TLR negative regulator) mRNA was observed after oligo-HA treatment of WT but not in Tlr4−/− macrophages, and oligo-HA did not suppress cytokine responsiveness in Traf1−/− macrophages. These results show that oligo-HA acts through TLR4 and TRAF1 to inhibit TLR3-dependent inflammation. This observation illustrates the complex immunomodulatory action of endogenous products released after injury.
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DOI：
10.1084/jem.20001858
发表时间：
2002-01-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Termeer C;Benedix F;Sleeman J;Fieber C;Voith U;Ahrens T;Miyake K;Freudenberg M;Galanos C;Simon JC
通讯作者：
Simon JC
影响因子：
33.6
作者：
Jiang D;Liang J;Noble PW
通讯作者：
Noble PW
影响因子：
158.5
作者：
Plenge, Robert M.;Seielstad, Mark;Gregersen, Peter K.
通讯作者：
Gregersen, Peter K.
影响因子：
5.4
作者：
Su, XQ;Li, S;Shu, HB
通讯作者：
Shu, HB
影响因子：
30.5
作者：
Boone, DL;Turer, EE;Ma, A
通讯作者：
Ma, A