Sphingosine kinase 1 and sphingosine 1-phosphate receptor 3 are functionally upregulated on astrocytes under pro-inflammatory conditions.
Sphingosine kinase 1 and sphingosine 1-phosphate receptor 3 are functionally upregulated on astrocytes under pro-inflammatory conditions.
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在促炎条件下，星形胶质细胞上的鞘氨醇激酶 1 和鞘氨醇 1-磷酸受体 3 功能上调。
DOI：
10.1371/journal.pone.0023905
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Pouly S
中科院分区：
文献类型：
--
作者：
Fischer I;Alliod C;Martinier N;Newcombe J;Brana C;Pouly S
反应性星形胶质细胞参与脱髓鞘疾病多发性硬化（MS）中神经炎症的发展和维持。鞘氨醇激酶1（SphK 1）/鞘氨醇1-磷酸（S1 P）受体信号通路参与许多细胞类型中炎症反应的调节，但S1 P受体亚型3（S1 P3）信号传导和SphK 1在活化的大鼠星形胶质细胞中的作用尚未确定。使用免疫组化，我们观察到S1 P3和SphK 1的表达上调的反应性星形胶质细胞和SphK 1的巨噬细胞在MS病变。用促炎刺激物脂多糖（LPS）处理大鼠原代星形胶质细胞培养物后，分别通过qPCR和Western印迹法测量，观察到S1 P3和SphK 1的mRNA和蛋白表达增加。通过SphK活性测定证实了LPS刺激对SphK的激活，并通过使用SphK抑制剂SKI（2-（p-羟基苯胺基）-4-（p-氯苯基）噻唑）来阻断。用选择性S1 P3激动剂处理星形胶质细胞导致细胞外信号调节激酶（ERK）-1/2的磷酸化增加，其在LPS预攻击下进一步升高，表明S1 P3上调可导致功能增加。此外，星形胶质细胞迁移在划痕试验中诱导的S1 P和LPS，这种LPS诱导的迁移是敏感的SphK 1的抑制，和独立的细胞增殖。此外，S1 P诱导潜在的神经保护性趋化因子CXCL 1的分泌，当星形胶质细胞用LPS预攻击时，CXCL 1的分泌增加。通过使用选择性S1 P3或S1 P1激动剂，证明了S1 P3信号传导比S1 P1信号传导更突出的作用。总之，我们的数据表明，当星形胶质细胞被LPS激活时，SphK 1/S1 P3信号轴被上调。这种信号通路似乎在星形胶质细胞活化的建立和维持中起作用。MS中该途径的上调可能是有害的，例如通过增强星形胶质细胞增生，或通过经由CXCL 1增加髓鞘再生而有益。
Reactive astrocytes are implicated in the development and maintenance of neuroinflammation in the demyelinating disease multiple sclerosis (MS). The sphingosine kinase 1 (SphK1)/sphingosine1-phosphate (S1P) receptor signaling pathway is involved in modulation of the inflammatory response in many cell types, but the role of S1P receptor subtype 3 (S1P3) signaling and SphK1 in activated rat astrocytes has not been defined. Using immunohistochemistry we observed the upregulation of S1P3 and SphK1 expression on reactive astrocytes and SphK1 on macrophages in MS lesions. Increased mRNA and protein expression of S1P3 and SphK1, as measured by qPCR and Western blotting respectively, was observed after treatment of rat primary astrocyte cultures with the pro-inflammatory stimulus lipopolysaccharide (LPS). Activation of SphK by LPS stimulation was confirmed by SphK activity assay and was blocked by the use of the SphK inhibitor SKI (2-(p-hydroxyanilino)-4-(p-chlorphenyl) thiazole. Treatment of astrocytes with a selective S1P3 agonist led to increased phosphorylation of extracellular signal-regulated kinase (ERK)-1/2), which was further elevated with a LPS pre-challenge, suggesting that S1P3 upregulation can lead to increased functionality. Moreover, astrocyte migration in a scratch assay was induced by S1P and LPS and this LPS-induced migration was sensitive to inhibition of SphK1, and independent of cell proliferation. In addition, S1P induced secretion of the potentially neuroprotective chemokine CXCL1, which was increased when astrocytes were pre-challenged with LPS. A more prominent role of S1P3 signaling compared to S1P1 signaling was demonstrated by the use of selective S1P3 or S1P1 agonists. In summary, our data demonstrate that the SphK1/S1P3 signaling axis is upregulated when astrocytes are activated by LPS. This signaling pathway appears to play a role in the establishment and maintenance of astrocyte activation. Upregulation of the pathway in MS may be detrimental, e.g. through enhancing astrogliosis, or beneficial through increased remyelination via CXCL1.
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影响因子：
4.8
作者：
Brinkmann, V;Davis, MD;Lynch, KR
通讯作者：
Lynch, KR
影响因子：
3.3
作者：
Kanno, T.;Nishizaki, T.;Nakamura, S.
通讯作者：
Nakamura, S.
DOI：
10.1016/j.bbrc.2007.02.043
发表时间：
2007-04-20
影响因子：
3.1
作者：
Lin, Chi-Iou;Chen, Chiung-Nien;Lee, Hsinyu
通讯作者：
Lee, Hsinyu
影响因子：
4.8
作者：
Kawamori, Toshihiko;Kaneshiro, Tatsuya;Obeid, Lina M.
通讯作者：
Obeid, Lina M.
影响因子：
6.2
作者：
Bassi, R;Anelli, V;Riboni, L
通讯作者：
Riboni, L