Lipopolysaccharide induces inflammatory hyperalgesia triggering a TLR4/MyD88-dependent cytokine cascade in the mice paw.
Lipopolysaccharide induces inflammatory hyperalgesia triggering a TLR4/MyD88-dependent cytokine cascade in the mice paw.
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DOI：
10.1371/journal.pone.0090013
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Verri WA Jr
中科院分区：
文献类型：
--
作者：
Calil IL;Zarpelon AC;Guerrero AT;Alves-Filho JC;Ferreira SH;Cunha FQ;Cunha TM;Verri WA Jr
炎症性疼痛可由不同的刺激引起，如创伤、辐射、抗原和感染。在感染引起的炎症性疼痛模型中，在小鼠爪中注射脂多糖（LPS），一种toll样受体4 （TLR4）激动剂，产生机械性痛觉过敏。我们在这里确定了引发这种反应的TLR4相关信号通路。首先，在野生型（WT）小鼠中注射LPS会产生机械性痛觉过敏，而在TRIF-/-小鼠中没有改变。另一方面，这种反应在TLR4突变和MyD88缺失的小鼠中不存在，在TNFR1缺失的小鼠中减少。IL-1受体拮抗剂、抗kc /CXCL1抗体、吲哚美辛或胍乙啶注射液也能减轻这种反应。此外，lps诱导小鼠爪中TNF-α、KC/CXCL1和IL-1β表达的时间依赖性增加，而这些在TLR4突变小鼠和MyD88缺失小鼠中不存在。此外，在TNFR1缺陷小鼠中，lps诱导的KC/CXCL1和IL-1β释放的升高低于野生型小鼠。LPS还诱导爪皮髓过氧化物酶活性增加，在TLR4突变小鼠和MyD88缺失小鼠中被抑制，而在TRIF-/-小鼠中没有改变。这些结果表明，lps诱导的小鼠炎症性疼痛仅依赖于TLR4/MyD88信号通路，而不是TLR4/TRIF信号通路。该途径触发感知细胞因子TNF-α释放，进而介导KC/CXCL1和IL-1β表达升高。最后，这些细胞因子可能参与刺激产生直接作用的痛觉介质，如前列腺素和拟交感神经胺。
Inflammatory pain can be triggered by different stimuli, such as trauma, radiation, antigen and infection. In a model of inflammatory pain caused by infection, injection in the mice paw of lipopolysaccharide (LPS), a Toll-like receptor 4 (TLR4) agonist, produces mechanical hyperalgesia. We identify here the TLR4 linked signaling pathways that elicit this response. Firstly, LPS paw injection in wild type (WT) mice produced mechanical hyperalgesia that was not altered in TRIF-/- mice. On the other hand, this response was absent in TLR4 mutant and MyD88 null mice and reduced in TNFR1 null mice. Either an IL-1 receptor antagonist, anti-KC/CXCL1 antibody, indomethacin or guanethidine injection also lessened this response. Moreover, LPS-induced time dependent increases in TNF-α, KC/CXCL1 and IL-1β expression in the mice paw, which were absent in TLR4 mutant and MyD88 null mice. Furthermore, in TNFR1 deficient mice, the LPS-induced rises in KC/CXCL1 and IL-1β release were less than in their wild type counterpart. LPS also induced increase of myeloperoxidase activity in the paw skin, which was inhibited in TLR4 mutant and MyD88 null mice, and not altered in TRIF-/- mice. These results suggest that LPS-induced inflammatory pain in mice is solely dependent on the TLR4/MyD88 rather than the TLR4/TRIF signaling pathway. This pathway triggers pronociceptive cytokine TNF-α release that in turn mediates rises in KC/CXCL1 and IL-1β expression. Finally, these cytokines might be involved in stimulating production of directly-acting hyperalgesic mediators such as prostaglandins and sympathomimetic amine.
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影响因子：
4.4
作者：
Gais, Petra;Tiedje, Christopher;Holzmann, Bernhard
通讯作者：
Holzmann, Bernhard
影响因子：
5.5
作者：
Guerrero, Ana T. G.;Verri, Waldiceu A., Jr.;Ferreira, Sergio H.
通讯作者：
Ferreira, Sergio H.
影响因子：
7.3
作者：
CUNHA, FQ;POOLE, S;FERREIRA, SH
通讯作者：
FERREIRA, SH
影响因子：
5.5
作者：
Cunha, Thiago M.;Verri, Waldiceu A., Jr.;Cunha, Fernando Q.
通讯作者：
Cunha, Fernando Q.
DOI：
10.1073/pnas.0409225102
发表时间：
2005-02-01
影响因子：
11.1
作者：
Cunha, TM;Verri, WA;Ferreira, SH
通讯作者：
Ferreira, SH