An ADP ribosylation factor-GTPase activating protein negatively regulates the production of proinflammatory mediators in response to lipopolysaccharide
An ADP ribosylation factor-GTPase activating protein negatively regulates the production of proinflammatory mediators in response to lipopolysaccharide
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DOI：
10.1007/s00262-011-1048-9
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发表时间：
2011-10-01
影响因子：
5.8
通讯作者：
Yokochi, Takashi
中科院分区：
文献类型：
--
作者：
Haque, Abedul;Noman, Abu Shadat Mohammod;Yokochi, Takashi
ADP核糖基化因子- gtpase激活蛋白（ASAP1）在多种肿瘤细胞中高表达，参与细胞的运动、侵袭和转移。为了阐明ASAP1在脂多糖（LPS）介导的炎症反应中的作用，我们利用RAW 264.7巨噬细胞样细胞研究了ASAP1沉默对脂多糖诱导的促炎介质产生的影响。ASAP1在细胞中组成性表达，并通过LPS刺激增强表达。用小干扰RNA沉默ASAP1可增强LPS对肿瘤坏死因子- α、白细胞介素6、干扰素- β和一氧化氮的产生。ASAP1沉默增强了核因子(NF)- κ B和几种丝裂原活化蛋白激酶（MAPKs）的激活。另一方面，ASAP1沉默不影响NF-kappa B信号上游分子IRAK4、TRAF6和Akt的表达。一系列toll样受体配体和LPS增强了ASAP1的表达。综上所述，ASAP1可能通过下调LPS信号传导负向调节LPS诱导的促炎介质的产生。讨论了ASAP1在脂多糖介导的炎症反应中的反馈作用。
An ADP ribosylation factor-GTPase activating protein (ASAP1) is highly expressed in a variety of tumor cells and is involved in the cell motility, invasion, and metastasis. In order to elucidate the involvement of ASAP1 in lipopolysaccharide (LPS)-mediated inflammatory response, the effect of ASAP1 silencing on LPS-induced proinflammatory mediators production was examined by using RAW 264.7 macrophage-like cells. ASAP1 was constitutively expressed in the cells and the expression was augmented by LPS stimulation. Silencing of ASAP1 with small interfering RNA enhanced the production of tumor necrosis factor-alpha, interleukin 6, interferon-beta, and nitric oxide in response to LPS. ASAP1 silencing augmented the activation of nuclear factor (NF)-kappa B and several mitogen-activated protein kinases (MAPKs). On the other hand, ASAP1 silencing did not affect the expression of IRAK4, TRAF6, and Akt as the upstream molecules of NF-kappa B signaling. A series of toll-like receptor ligands as well as LPS augmented the ASAP1 expression. Taken together, ASAP1 was suggested to negatively regulate LPS-induced proinflammatory mediators production through down-regulating LPS signaling. The feedback function of ASAP1 in LPS-mediated inflammatory response is discussed.