NFκB Activation in Mouse Pituitary: Comparison of Response to Interleukin-1β and Lipopolysaccharide

Abstract

The mouse anterior pituitary contains both types of interleukin (IL)-1 receptors, IL-1 receptor type I (IL-1RI) and IL-1 receptor type II (IL-1RII). These receptors are expressed mainly on somatotroph cells. In the present study, the ability of the mouse pituitary to respond in vivo to IL-1 or to lipopolysaccharide (LPS) was demonstrated by measuring, with an electrophoretic mobility shift assay, the presence of an active NF kappa B complex in cell nuclei from pituitaries of mice injected intraperitoneally with recombinant rat-IL-1 beta or LPS. Using immunohistochemistry with an antibody directed against the p65 NF kappa B subunit, a rapid and transient NF kappa B response to LPS was observed. This response was present predominantly in the nuclei of glial fibrillary acidic protein (GFAP)-positive cells and F4/80-labelled cells of the posterior and the anterior pituitary 15 min after stimulation and became faint after 2 h. In comparison, the early and strong NF kappa B response to IL-1 beta treatment was localized into somatotroph cells, GFAP positive cells and F4/80-labelled cells of the posterior and anterior pituitary. Activation of NF kappa B in response to IL-1 beta was no longer apparent in IL-1RI knockout mice, confirming that this receptor is essential for the transduction of IL-1 signal in the pituitary, but remained after LPS treatment. In addition, we investigated the effect of IL-1 on target genes by measuring the mRNA and proteins synthesis of growth hormone (GH), IL-6 and IL-1ra in the pituitary and the plasma. IL-1 beta was shown to induce a rapid and strong synthesis of IL-6 and IL-1ra in the pituitary but failed to regulate GH contents or release. These data suggest that the pituitary is able to respond to a systemic infection via cytokine-mediated responses transduced by IL-1.