Distinct roles of prostaglandin H synthases 1 and 2 in T-cell development
Distinct roles of prostaglandin H synthases 1 and 2 in T-cell development
复制标题
DOI：
10.1172/jci6400
复制
发表时间：
1999-05-01
影响因子：
15.9
通讯作者：
FitzGerald, GA
中科院分区：
文献类型：
--
作者：
Rocca, B;Spain, LM;FitzGerald, GA
前列腺素G和H结合酶或环氧合酶（COX）催化前列腺素（PG）的形成。考克斯-1在胚胎15.5天胸腺的淋巴样细胞中弥散表达，而考克斯-2表达稀少，明显限于基质细胞。相比之下，考克斯-2主要存在于3 - 5周龄小鼠的骨髓基质细胞亚群中。同工酶对淋巴细胞发育的贡献也不同。因此，在正常小鼠和重组酶激活基因-1敲除小鼠的胸腺叶中使用选择性考克斯-1抑制剂的实验支持了该同种型在从CD 4（-）CD 8（-）双阴性（DN）到CD 4（+）CD 8（+）双阳性（DP）的转变中的作用。在COX-I敲除中获得一致的数据。相反，考克斯-2的药理学抑制和基因缺失支持其在早期胸腺细胞增殖和分化过程中以及随后在CD 4辅助T细胞谱系成熟过程中的作用。PGE（2），而不是其他PG，可以挽救任何一种亚型的抑制作用，尽管它通过不同的EP受体亚型发挥作用。COX依赖性PG的产生可能是胸腺基质支持T细胞发育的一种机制。
Prostaglandin G and H synthases, or cyclooxygenases (COXs), catalyze the formation of prostaglandins (PGs). Whereas COX-1 is diffusely expressed in lymphoid cells in embryonic day 15.5 thymus, COX-2 expression is sparse, apparently limited to stromal cells. By contrast, COX-2 is predominant in a subset of medullary stromal cells in three- to five-week-old mice. The isozymes also differ in their contributions to lymphocyte development. Thus, experiments with selective COX-1 inhibitors in thymic lobes from normal and recombinase-activating gene-1 knockout mice support a role for this isoform in the transition from CD4(-)CD8(-) double-negative (DN) to CD4(+)CD8(+) double-positive (DP). Concordant data were obtained in COX-I knockouts. Pharmacological inhibition and genetic deletion of COX-2, by contrast, support its role during early thymocyte proliferation and differentiation and, later, during maturation of the CD4 helper T-cell Lineage. PGE(2), but not other PGs, can rescue the effects of inhibition of either isoform, although it acts through distinct EP receptor subtypes. COX-dependent PG generation may represent a mechanism of thymic stromal support for T-cell development.