Diel Variation in CC Chemokine Gene Expression in the Japanese Pufferfish Takifugu rubripes.

Abstract

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.