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 E-2(PGE(2)) exhibited dose-dependent inhibition of the antigen presenting molecules major histocompatability class I and II and the pro-inflammatory cytokine interleukin-1 beta gene expression. Prostaglandin E-2 was found to be stimulatory towards cyclooxygenase-2 (COX-2) expression at higher concentrations (1 x 10(-6) and 1 x 10(-8) M) and inhibitory at lower concentrations (1 x 10(-10) and 1 x 10(-12) M) after 4h exposure. After 24 h exposure, however, LPS-induced COX-2 expression decreased and was completely inhibited by all PGE2 concentrations (1 x 10(-6)-1 x 10(-10) m). Incubation of SHK-1 cells with LPS alone had no effect on tumour necrosis factor alpha (TNF alpha)-like gene or transforming growth factor beta-like gene expression after 4 h, however, LPS and PGE2 showed a synergistic effect on TNF alpha-like gene expression after 24 h. This study provides evidence for the existence of a PGE(2)-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-1 beta. 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. (c) 2005 Elsevier Ltd. All rights reserved.