Lipopolysaccharide and pneumococcal cell wall components activate the mitogen activated protein kinases (MAPK) erk‐1, erk‐2, and p38 in astrocytes
Lipopolysaccharide and pneumococcal cell wall components activate the mitogen activated protein kinases (MAPK) erk‐1, erk‐2, and p38 in astrocytes
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脂多糖和肺炎球菌细胞壁成分激活星形胶质细胞中的丝裂原激活蛋白激酶 (MAPK) erk-1、erk-2 和 p38
作者：
Ralf R. Schumann;D. Pfeil;D. Freyer;W. Buerger;N. Lamping;C. Kirschning;Ulf B. Goebel;J. Weber
革兰氏阳性细菌的细胞壁化合物能够像革兰氏阴性细菌的脂多糖（LPS）一样，诱导CNS细胞中促炎细胞因子的生物合成。缺乏CD14脂多糖受体的星形胶质细胞也被证明通过增加细胞因子合成来响应脂多糖刺激。然而，在这个过程中涉及的信号步骤几乎一无所知。因此，我们研究了LPS和肺炎球菌细胞壁（PCW）在大鼠星形胶质细胞和人星形细胞瘤细胞系U373MG原代培养中的信号事件。我们特别感兴趣的是有丝分裂原活化蛋白激酶（MAPK）家族的三个成员的酪氨酸磷酸化模式和激活状态，即细胞外信号调节蛋白激酶（erk）‐1、erk‐2和最近发现的p38。我们发现LPS和PCW以剂量依赖的方式启动酪氨酸磷酸化和erk‐1、erk‐2和p38的激活。酪氨酸磷酸化抑制剂能够减轻这种影响，并阻断星形胶质细胞的细胞因子产生。LPS和PCW诱导的星形细胞反应都需要血清中存在可溶性CD14 （sCD14）。揭示细菌化合物在中枢神经系统细胞中诱导的信号传导步骤可能有助于阐明脑膜炎和败血症的中枢神经并发症的病理机制，并可能为新的治疗策略提供选择。《圣经》22:29 - 305,1998。©1998 Wiley‐Liss, Inc。
Cell wall compounds of gram‐positive bacteria are capable of inducing the biosynthesis of proinflammatory cytokines in CNS cells in a similar way as lipopolysaccharide (LPS) of gram‐negative bacteria does. Astrocytes, which lack the CD14 LPS receptor, have also been shown to respond to LPS‐stimulation by increased cytokine synthesis. However, almost nothing is known about signaling steps involved in this process. We have therefore examined signaling events in primary cultures of rat astrocytes and the human astrocytoma cell line U373MG, brought about by LPS and pneumococcal cell walls (PCW). Of particular interest to us was the tyrosine phosphorylation patterns and activation states of three members of the mitogen activated protein kinase (MAPK) family, i.e., extracellular signal‐regulated protein kinase (erk)‐1, erk‐2, and the recently identified p38. We show that LPS and PCW initiate tyrosine phosphorylation and activation of erk‐1, erk‐2, and p38 in a dose‐dependent fashion. Inhibitors of tyrosine phosphorylation were able to alleviate this effect and also blocked cytokine production of astrocytes. Both, LPS‐ and PCW‐induced responses of astrocytic cells required the presence of soluble CD14 (sCD14) present in serum. Unraveling the signaling steps induced by bacterial compounds in cells of the CNS may potentially help to elucidate the pathomechanisms of meningitis and central nervous complications of sepsis and may offer options for novel treatment strategies. GLIA 22:295–305, 1998. © 1998 Wiley‐Liss, Inc.
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影响因子：
56.9
作者：
SCHUMANN, RR;LEONG, SR;ULEVITCH, RJ
通讯作者：
ULEVITCH, RJ
影响因子：
56.9
作者：
HAN, J;LEE, JD;ULEVITCH, RJ
通讯作者：
ULEVITCH, RJ
影响因子：
56.9
作者：
WRIGHT, SD;RAMOS, RA;MATHISON, JC
通讯作者：
MATHISON, JC
DOI：
10.1073/pnas.88.10.4148
发表时间：
1991-05
影响因子：
11.1
作者：
S. L. Weinstein;M. Gold;A. DeFranco
通讯作者：
S. L. Weinstein;M. Gold;A. DeFranco
DOI：
10.1073/pnas.90.7.2744
发表时间：
1993-04-01
影响因子：
11.1
作者：
PUGIN, J;SCHURERMALY, CC;TOBIAS, PS
通讯作者：
TOBIAS, PS