The Toll-like receptor 1/2 agonists Pam3CSK4 and human β-defensin-3 differentially induce interleukin-10 and nuclear factor-κB signalling patterns in human monocytes
The Toll-like receptor 1/2 agonists Pam3CSK4 and human β-defensin-3 differentially induce interleukin-10 and nuclear factor-κB signalling patterns in human monocytes
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DOI：
10.1111/j.1365-2567.2011.03475.x
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发表时间：
2011-10-01
期刊：
影响因子：
6.4
通讯作者：
Sieg, Scott F.
中科院分区：
文献类型：
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作者：
Funderburg, Nicholas T.;Jadlowsky, Julie K.;Sieg, Scott F.
人β-防御素3（hBD-3）通过Toll样受体（TLR）1/2激活抗原呈递细胞。已经鉴定了几种TLR 1/2激动剂，但关于它们如何差异地影响细胞活化知之甚少。我们比较了hBD-3与另一种TLR 1/2激动剂Pam（3）CSK（4）在人单核细胞中的作用。与hBD-3或Pam（3）CSK（4）孵育的单核细胞产生白细胞介素-6（IL-6）、IL-8和IL-1 β，但只有Pam（3）CSK（4）诱导IL-10。Pam（3）CSK（4）诱导的IL-10导致共刺激分子CD 86下调，而暴露于hBD-3的单核细胞中CD 86表达增加。对与IL-10诱导相关的信号传导途径的评估表明，hBD-3或Pam（3）CSK（4）类似地激活了丝裂原活化蛋白激酶，而非经典核因子-κ B途径仅由Pam（3）CSK（4）诱导。我们的数据表明，hBD-3缺乏非典型的核因子-κ B信号传导可能导致TLR激动剂在人单核细胞中诱导产生抗炎细胞因子IL-10的失败。
Human beta-defensin 3 (hBD-3) activates antigen-presenting cells through Toll-like receptors (TLRs) 1/2. Several TLR1/2 agonists have been identified but little is known about how they might differentially affect cellular activation. We compared the effects of hBD-3 with those of another TLR1/2 agonist, Pam(3)CSK(4), in human monocytes. Monocytes incubated with hBD-3 or Pam(3)CSK(4) produced interleukin-6 (IL-6), IL-8 and IL-1 beta, but only Pam(3)CSK(4) induced IL-10. The IL-10 induction by Pam(3)CSK(4) caused down-modulation of the co-stimulatory molecule, CD86, whereas CD86 expression was increased in monocytes exposed to hBD-3. Assessment of signalling pathways linked to IL-10 induction indicated that mitogen- activated protein kinases were activated similarly by hBD-3 or Pam(3)CSK(4), whereas the non-canonical nuclear factor-kappa B pathway was only induced by Pam(3)CSK(4). Our data suggest that the lack of non-canonical nuclear factor-kappa B signalling by hBD-3 could contribute to the failure of this TLR agonist to induce production of the anti-inflammatory cytokine, IL-10, in human monocytes.