Hypoxia-inducible factor-1α involved in macrophage regulation in ayu (Plecoglossus altivelis) under hypoxia

Hypoxia-inducible factor-1 alpha (HIF-1 alpha) plays a critical role in immune and inflammatory responses and is important in controlling a variety of processes in monocytes and macrophages. However, the role of HIF-1 alpha in the teleost immune system remains less known. In this study, we cloned the cDNA sequence of HIF-1 alpha from the ayu (Plecoglossus altivelis, PaHIF-1 alpha). Sequence and phylogenetic tree analysis showed that PaHIF-1 alpha clustered within the fish HIF-1 alpha tree and was closely related to that of Northern pike (Esox Lucius). PaHIF-1 alpha was expressed in all tested tissues and expression increased in liver, head kidney, and body kidney upon Vibrio anguillarum infection. PaHIF-1 alpha was found to regulate the expression of cytokines in ayu monocytes/macrophages (MO/M Phi). PaHIF-1 alpha mediated hypoxia-induced enhancement of MO/M Phi phagocytic and bactericidal activities to enhance host defenses. Compared with the control, intermittent hypoxia further increased the expression of PaHIF-1 alpha mRNA, improved the survival rate, and reduced the bacterial load of V. anguillarum-infected ayu. Therefore, PaHIF-1 alpha may play a predominant role in the modulation of ayu MO/M Phi function.