Prostaglandin E₂ modulation of gene expression in an Atlantic salmon (Salmo salar) macrophage-like cell line (SHK-1)

Following lipopolysaccharide (LPS)-stimulation of Atlantic salmon (Salmo salar) macrophage-like SHK-1 cells, prostaglandin E₂ (PGE ₂) exhibited dose-dependent inhibition of the antigen presenting molecules major histocompatability class I and II and the pro-inflammatory cytokine interleukin-1β gene expression. Prostaglandin E₂ was found to be stimulatory towards cyclooxygenase-2 (COX-2) expression at higher concentrations (1×10^-6 and 1×10^-8 M) and inhibitory at lower concentrations (1×10^-10 and 1×10 ^-12 M) after 4 h exposure. After 24 h exposure, however, LPS-induced COX-2 expression decreased and was completely inhibited by all PGE₂ concentrations (1×10^-6-1×10^-10 M). Incubation of SHK-1 cells with LPS alone had no effect on tumour necrosis factor α (TNFα)-like gene or transforming growth factor β-like gene expression after 4 h, however, LPS and PGE₂ showed a synergistic effect on TNFα-like gene expression after 24 h. This study provides evidence for the existence of a PGE₂-mediated negative feedback mechanism in the control of PGs through down-regulation of COX-2, as well as for inflammatory responses by the down-regulation of both COX-2 and IL-1β. The differential regulation of immune-related genes under these conditions further demonstrates the usefulness of the SHK-1 cell line for studying aspects of salmonid immunology.