CC chemokines are key molecules in the regulation of leukocyte trafficking to the site of injury, infection, or inflammation. In recent years, some mammalian chemokines have been shown to exhibit rhythmic expression, regulated by clock genes. However, the rhythmic expression of chemokines in teleost fish remains unknown. In the present study, the diel variation of teleost CC chemokine genes was investigated using the model fish, Fugu (Takifugu rubripes). Diel variation analysis revealed that clock (bmal1, clock1, per2, rorα, and rev-erbβ) and CC chemokine (ccl18l, ccl19, and ccl25l) genes show diel expression under 12:12 light-dark cycle (LD12:12) conditions. CC chemokine genes, which exhibit diel expression, contain RORE (ccl18l, ccl19, ccl25l) and/or E-box (ccl25l) motifs in their transcription regulatory region. Moreover, in vitro head kidney stimulation with lipopolysaccharide (LPS) at different zeitgeber times (ZT) under LD12:12 conditions affected the degree of ccl18l, ccl19, and ccl25l expression; high and low responsiveness to LPS stimulation at ZT12 and ZT0 (ccl25l), and ZT16 and ZT4 (ccl18l and ccl19), respectively, were observed. These results suggest that the expression of some fish CC chemokines is affected by the diel variation regulated by clock proteins, and that responsiveness against bacterial infection depends on the time zone.

CC趋化因子是调节白细胞向损伤，感染或炎症部位运输的关键分子。近年来，一些哺乳动物趋化因子已显示出受时钟基因调节的节律性表达。然而，在硬骨鱼中趋化因子的节律性表达仍然未知。在本研究中，使用模型鱼Fugu（Takifugu rubripes）研究了硬骨CC趋化因子基因的diel变异。Diel变异分析显示Clock（bmal1，clock1，per2，rorα和rev-erbβ）和CC趋化因子（ccl18l，ccl19和ccl25l基因在12:12的明暗循环（LD12：12）条件下显示diel表达。展示diel表达的CC趋化因子基因在其转录调控区含有RORE（ccl18l，ccl19，ccl25l）和/或E-box（ccl25l）基序。此外，在LD12：12条件下，在不同的Zeitgeber时间（ZT）用脂多糖（LPS）体外刺激头部肾脏会影响ccl18l，ccl19和ccl25l的表达程度。ZT12和ZT0（ccl25l）以及ZT16和ZT4（ccl18l和ccl19）对LPS刺激的高和低反应性），分别进行观察。这些结果表明，某些鱼CC趋化因子的表达受时钟蛋白调节的diel变化的影响，并且对细菌感染的反应性取决于时区。