The interleukin-6 regulates the function of monocytes/macrophages (MO/MΦ) via the interleukin-6 receptor β in ayu (Plecoglossus altivelis)

Interleukin-6 (IL-6) is one of the most pleiotropic cytokines because of its wide range of effects on cells of the immune and non-immune systems in the body. However, the role of IL-6 in fish monocytes/macrophages (MO/M Phi) is poorly understood. In this study, we cloned the cDNA sequence of the IL-6 gene from ayu (Plecoglossus altivelis) and demonstrated using a tissue distribution assay that ayu interleukin-6 (PaIL-6) mRNA is expressed in all tested tissues. Changes in expression were observed in immune tissues as well as in MO/M Phi after a Vibrio anguillarum infection; subsequently, PaIL-6 was expressed and purified to prepare anti-PaIL-6 antibodies. Recombinant PaIL-6 protein (rPaIL-6) treatment enhanced pro-inflammatory cytokine expression. Ayu interleukin-6 receptor (PaIL-6R beta) knockdown resulted in decreased pro-inflammatory cytokine expression in MO/ M Phi treated with rPaIL-6, whereas no significant changes were observed after ayu interleukin-6 receptor a (PaIL-6R alpha) knockdown in MO/M Phi. PaIL-6 and PaIL-6R beta knockdown in MO/M Phi inhibited the phosphorylation of signal transducer and activator of transcription 1. Moreover, PaIL-6R beta knockdown inhibited the phagocytic and bactericidal ability of ayu MO/Mm treated with rPaIL-6. These data indicate that PaIL-6 may be able to regulate the function of ayu MO/M Phi.