Anti- and Proinflammatory Effects of 15-Deoxy-Δ12,14-Prostaglandin J2(15d-PGJ2) on Human Eosinophil Functions
Anti- and Proinflammatory Effects of 15-Deoxy-Δ12,14-Prostaglandin J2(15d-PGJ2) on Human Eosinophil Functions
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DOI：
10.1159/000101399
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发表时间：
2007-05
影响因子：
2.8
通讯作者：
S. Ueki;H. Kato;Yoshiki Kobayashi;W. Ito;T. Adachi;H. Nagase;K. Ohta;H. Kayaba;J. Chihara
中科院分区：
文献类型：
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作者：
S. Ueki;H. Kato;Yoshiki Kobayashi;W. Ito;T. Adachi;H. Nagase;K. Ohta;H. Kayaba;J. Chihara
环戊烯酮前列腺素15-deoxy-Δ12,14-前列腺素J2 （15d-PGJ2）被认为是一种有效的脂质介质，来源于过敏性炎症部位大量产生的PGD2。现在已经确定15d-PGJ2通过其细胞内靶点如过氧化物酶体增殖物激活受体-γ (PPARγ)负调控细胞功能。然而，最近的研究表明，15d-PGJ2似乎不仅具有抗炎活性，而且还具有促炎潜能，这取决于其浓度和靶细胞的激活状态。例如，在低浓度下，15d-PGJ2通过与PPARγ的连接增强eotaxin诱导的嗜酸性粒细胞的趋化性、形状变化和肌动蛋白重组。此外，15d-PGJ2本身是一种强效的趋化剂，通过其在Th2细胞上表达的膜受体-趋化受体同源分子（CRTH2）诱导钙动员，上调CD11b的表达。相反，在高浓度下，15d-PGJ2通过诱导细胞凋亡以不依赖ppar γ的方式抑制嗜酸性粒细胞存活。在这里，我们讨论了15d-PGJ2的病理生理作用，它可以作为旁分泌、自分泌和分泌内物质来调节嗜酸性粒细胞的功能。
The cyclopentenone prostaglandin 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) is recognized as a potent lipid mediator that is derived from PGD2, which is produced abundantly in allergic inflammatory sites. It is now established that 15d-PGJ2 negatively regulates cellular functions through its intracellular targets such as peroxisome proliferator-activated receptor-γ (PPARγ). However, recent studies revealed that 15d-PGJ2 appears to possess not only anti-inflammatory activities but also a proinflammatory potential depending on its concentration and the activation state of the target cell. For instance, at low concentrations, 15d-PGJ2 enhances eotaxin-induced chemotaxis, shape change, and actin reorganization in eosinophils through its ligation with PPARγ. Moreover, 15d-PGJ2 itself is a potent chemoattractant, and it induces calcium mobilization, and up-regulates CD11b expression through its membrane receptor – chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2). Conversely, at high concentrations, 15d-PGJ2 inhibits eosinophil survival by inducing apoptosis in a PPARγ-independent manner. Here, we discuss the pathophysiological roles of 15d-PGJ2 that could act as a paracrine, autocrine, and intracrine substance to regulate eosinophil functions.