A cyclophilin A (CypA) from Apostichopus japonicus modulates NF-κB translocation as a cofactor

As a ubiquitously expressed protein, cyclophilin A (CypA) is involved in a variety of pathological process, including immune suppression, inflammation, cell apoptosis, viral infection and stress response. However, the functional roles of CypA were largely unknown in economic marine animals. In this report, a novel CypA gene from sea cucumber Apostichopus japonicus (designated as AjCypA) was cloned and its function roles in immune responses were explored. The full-length cDNA of AjCypA was 1297 bp containing an open reading frame of 489 bp encoding a putative protein of 162 amino acids (aa). A conserved cyclophilin-like domain (CLD) with PPIase signature was located from 5 to 155 aa sequences in AjCypA, in which five necessary aa residues was totally conserved. In healthy sea cucumbers, AjCypA was expressed in all detected tissues, with highly expressed in muscles and weakly expressed in coelomocytes. AjCypA transcripts was significantly induced 8.08-fold and 5.65-fold in coelomocytes when sea cucumbers challenged with Vibrio splendidus in vivo and LPS in vitro, respectively. The expression pattern is similar with the expression of AjRel in the same condition. Moreover, GST pull-down and immunofluorescence analysis both revealed that AjCypA might be interacted with AjRel. Furthermore, AjCypA knockdown not only inhibited the expression of inflammation cytokines, but also suppressed the translocation of AjRel in nucleus induced by LPS. Taken together, our results suggested that AjCypA play key roles in V. splendidus mediated immune responses via suppressing the nuclear translocation of AjRel activity in sea cucumber.