Pharma Research and Early Development, Hoffmann-La Roche Inc., Nutley, NJ 07110, USA.
Biomarkers. 2010 Nov;15(7):646-54. doi: 10.3109/1354750X.2010.511266. Epub 2010 Sep 21.
CRTH2 is one of the prostaglandin D₂ receptors and plays a proinflammatory role in allergic diseases. Gene expression markers in whole blood induced by CRTH2 activation have not previously been reported. Using microarray analyses of 54 675 genes, we revealed modest gene expression changes in human whole blood stimulated in vitro by a selective CRTH2 agonist, DK-PGD₂. Five genes were found to exhibit 1.5- to 2.6-fold changes in expression. The expression of Charcot-Leyden crystal protein/galectin-10 (CLC/Gal-10) in particular was consistently enhanced in human whole blood stimulated by DK-PGD₂, as confirmed by quantitative real-time polymerase chain reaction analyses. DK-PGD(2)-induced increases in blood CLC/Gal-10 mRNA levels were largely attenuated by the CRTH2 antagonist CAY10471.Thus, the DK-PGD₂-induced CLC/Gal-10 mRNA level can serve as a potential marker for monitoring pharmacodynamic effects of blood exposure to CRTH2 modulating agents.
CRTH2 是前列腺素 D2 受体之一,在过敏疾病中发挥促炎作用。CRTH2 激活诱导的全血基因表达标志物以前尚未报道过。通过对 54675 个基因的微阵列分析,我们揭示了体外选择性 CRTH2 激动剂 DK-PGD2 刺激人全血中的适度基因表达变化。发现有 5 个基因的表达发生了 1.5 到 2.6 倍的变化。特别是 Ch arcot-Leyden 晶体蛋白/半乳糖凝集素-10(CLC/Gal-10)的表达在 DK-PGD2 刺激的人全血中始终增强,这一点通过定量实时聚合酶链反应分析得到了证实。CRTH2 拮抗剂 CAY10471 大大减弱了 DK-PGD2 诱导的血液 CLC/Gal-10 mRNA 水平的增加。因此,DK-PGD2 诱导的 CLC/Gal-10 mRNA 水平可以作为监测血液接触 CRTH2 调节剂的药效学效应的潜在标志物。