Dexamethasone synergistically increases secretion of the anti-inflammatory cytokine interleukin(IL)-10 in murine dendritic cells (DCs) upon viral infection: Potential implication to stress-mediated modification of susceptibility to viral infection. (94.4)

Abstract

Abstract Glucocorticoids (GC) are end-products of the HPA axis, which play central roles in stress response, including pathogen infection, and are widely used as therapeutic agents for inflammatory diseases. It is known that stressed condition altered the susceptibility to viral infection. Since it is not known how GC influence the function of DCs upon viral infection, we infected murine DC with Newcastle disease virus (NDV) in the presence of glucocorticoid receptor (GR) ligand dexamethasone (Dex), and examined mRNA expression of 84 genes, which play various roles in the TLR signaling cascade. We found that NDV infection potently induced mRNA expression of 24 genes. Among them, 7 genes (interferon (IFN)-γ, interleukin (IL)-6, IL-10, lymphotoxin A, C-type lectin domain family 4, nuclear factor of κ light chain gene enhancer in B cell inhibitor β and prostaglandin-endoperoxidase synthase 2) were further up- or down-regulated by Dex pre-treatment. Particularly on IL-10, Dex synergistically up-regulated NDV-induced mRNA by 7-fold. The Dex effect was mediated by GR, as inhibitor RU 486 abolished the effect. In contrast to IFN-γ and IL-6, which are Th1 cytokines and response at early time point (6 h), kinetics of IL-10 mRNA showed the highest synergistic effect of NDV and Dex at a later time point (24 h). ELISA results showed consistent results with mRNA expression. Taken together, our study indicates that GC modulate host immunity, altering TLR-related gene expression in DCs.