Granulocyte colony-stimulating factor negatively regulates Toll-like receptor agonist-induced cytokine production in human neutrophils
Granulocyte colony-stimulating factor negatively regulates Toll-like receptor agonist-induced cytokine production in human neutrophils
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DOI：
10.1016/j.abb.2010.01.005
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发表时间：
2010-03-15
影响因子：
3.9
通讯作者：
Kitagawa, Seiichi
中科院分区：
文献类型：
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作者：
Fukuzono, Shunsuke;Kato, Takayuki;Kitagawa, Seiichi
我们研究了G-CSF对TLR激动剂诱导的人中性粒细胞中细胞因子产生的影响。人嗜中性粒细胞响应TLR激动剂如LPS和N-棕榈酰-S-[2，3-双（棕榈酰氧基）-（2 RS）-丙基]-（R）-半胱氨酰-丝氨酰-（赖氨酰）（3）-赖氨酸的刺激产生IL-8和TNF-α。这种反应依赖于ERK、p38和PI 3 K的激活，而不是JNK。TLR激动剂诱导的中性粒细胞中细胞因子的产生被G-CSF抑制，而被GM-CSF增强，并且GM-CSF介导的增强被G-CSF减弱。G-CSF和GM-CSF不影响TLR激动剂诱导的ERK、p38、JNK、Akt和I κ B α磷酸化。STAT 3在G-CSF刺激的中性粒细胞中的激活比在GM-CSF刺激的细胞中的激活大得多。用AG-490（JAK 2抑制剂）预处理细胞可阻止G-CSF介导的STAT 3磷酸化和TLR激动剂诱导的细胞因子产生抑制。这些发现表明G-CSF和GM-CSF对TLR激动剂诱导的细胞因子产生发挥相反的作用，并且G-CSF通过激活STAT 3负调节TLR激动剂诱导的中性粒细胞中的细胞因子产生。(C)2010年爱思唯尔公司All rights reserved.
We studied the effect of G-CSF on TLR agonist-induced cytokine production in human neutrophils. Human neutrophils produced IL-8 and TNF-alpha in response to stimulation with TLR agonists such as LPS and N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2RS)-propyl]-(R)-cysteinyl-seryl-(lysyl)(3)-lysine. This response was dependent on activation of ERK, p38, and PI3K, but not JNK. TLR agonist-induced cytokine production in neutrophils was inhibited by G-CSF, whereas it was enhanced by GM-CSF, and GM-CSF-mediated enhancement was attenuated by G-CSF. G-CSF and GM-CSF did not affect TLR agonist-induced phosphorylation of ERK, p38, JNK, Akt, and I kappa B alpha. STAT3 activation was much greater in G-CSF-stimulated neutrophils than that in GM-CSF-stimulated cells. G-CSF-mediated STAT3 phosphorylation and inhibition of TLR agonist-induced cytokine production were prevented by pretreatment of cells with AG-490 (JAK2 inhibitor). These findings suggest that G-CSF and GM-CSF exert the opposite effects on TLR agonist-induced cytokine production, and G-CSF negatively regulates TLR agonist-induced cytokine production in neutrophils via activation of STAT3. (C) 2010 Elsevier Inc. All rights reserved.