Activation of Different Heterodimers of TLR2 Distinctly Mediates Pain and Itch
Activation of Different Heterodimers of TLR2 Distinctly Mediates Pain and Itch
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TLR2 不同异二聚体的激活明显介导疼痛和瘙痒
DOI：
10.1016/j.neuroscience.2020.01.010
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发表时间：
2020-01
期刊：
影响因子：
3.3
通讯作者：
Ling Zhang
中科院分区：
文献类型：
--
作者：
Ting-Ting Wang;Xian-Yun Xu;Wei Lin;Dan-Dan Hu;Wu Shi;Xin Jia;Hui Wang;Ning-Jing Song;Yu-Qiu Zhang;Ling Zhang
Toll样受体（TLR）与疼痛和瘙痒调节有关。TLR 2是TLR家族成员，检测微生物膜成分，与病理性疼痛有关。然而，TLR 2在瘙痒和伤害性反应中的作用尚未得到彻底研究。本研究中，我们发现TLR 2在小鼠背根神经节（DRG）和三叉神经节（TG）神经元中表达。在TLR 2基因敲除（KO）小鼠中，瘙痒和疼痛行为，包括组胺依赖性和组胺非依赖性急性瘙痒、丙酮/乙醚/水和2，4-二硝基氟苯诱导的慢性瘙痒和炎性疼痛，在很大程度上减弱。靶向TLR 2/1异二聚体的TLR 2激动剂Pam 3CSK 4诱发疼痛和瘙痒行为，而识别TLR 2/6异二聚体的脂磷壁酸（LTA）和酵母聚糖仅产生疼痛反应。TLR 2激动剂诱导的伤害性和刺激性行为在瞬时受体电位香草素1（TRPV 1）和瞬时受体电位锚蛋白1（TRPA 1）KO小鼠中大大减少。最后，Pam 3Csk 4和酵母聚糖增加野生型小鼠DRG神经元中的[Ca 2 +] i。而TRPV 1和TRPA 1基因敲除小鼠DRG神经元内[Ca ~（2+）] i的增加则受到明显抑制。我们的研究结果表明，TLR 2通过TRPV 1和TRPA 1通道激活TLR 1/TLR 2或TLR 6/TLR 2异源二聚体参与不同的瘙痒和疼痛行为。
Toll-like receptors (TLRs) have been implicated in pain and itch regulation. TLR2, a TLR family member that detects microbial membrane components, has been implicated in pathologic pain. However, the role of TLR2 in pruritic and nociceptive responses has not been thoroughly investigated. In this study, we found that TLR2 was expressed in mouse dorsal root ganglia (DRG) and trigeminal ganglia (TG) neurons. Itch and pain behaviors, including histamine-dependent and histamine-independent acute itching, acetone/diethyl ether/water and 2,4-dinitrofluorobenzene-induced chronic itching and inflammatory pain, were largely attenuated in TLR2 knockout (KO) mice. The TLR2 agonist Pam3CSK4, which targets TLR2/1 heterodimers, evoked pain and itch behavior, whereas lipoteichoic acid (LTA) and zymosan, which recognize TLR2/6 heterodimers, produced only pain response. The TLR2 agonist-induced nociceptive and pruritic behaviors were largely diminished in transient receptor potential vanilloid 1 (TRPV1) and transient receptor potential ankyrin 1 (TRPA1) KO mice. Finally, Pam3Csk4 and zymosan increased the [Ca2+]iin DRG neurons from wild-type mice. However, the enhancement of [Ca2+]iwas largely inhibited in the DRG neurons from TRPV1 and TRPA1 KO mice. Our results demonstrate that TLR2 is involved in different itch and pain behaviors through activating TLR1/TLR2 or TLR6/TLR2 heterodimers via TRPV1 and TRPA1 channels.
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影响因子：
82.9
作者：
Xu ZZ;Kim YH;Bang S;Zhang Y;Berta T;Wang F;Oh SB;Ji RR
通讯作者：
Ji RR
DOI：
10.4049/jimmunol.1001241
发表时间：
2011-06-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Qi J;Buzas K;Fan H;Cohen JI;Wang K;Mont E;Klinman D;Oppenheim JJ;Howard OM
通讯作者：
Howard OM
影响因子：
1.4
作者：
M. Sakamoto;R. Asahina;H. Kamishina;S. Maeda
通讯作者：
M. Sakamoto;R. Asahina;H. Kamishina;S. Maeda
TLR1/TLR2异二聚体在识别伯氏螺旋体中起着重要作用。
影响因子：
3.7
作者：
Oosting M;Ter Hofstede H;Sturm P;Adema GJ;Kullberg BJ;van der Meer JW;Netea MG;Joosten LA
通讯作者：
Joosten LA
影响因子：
5.6
作者：
Liu, Tong;Gao, Yong-Jing;Ji, Ru-Rong
通讯作者：
Ji, Ru-Rong