Expression of functionally active NOD1 and NOD2 in folliculostellate TtT/GF pituitary cells

Abstract

The follicullostellate (FS) cells of the pituitary share properties with dendritic cells and also with macrophages. A contingent of FS cells express MHC class I and MHC class II molecules and also several lymphoid markers and lymphatic markers. Therefore, FS cells were found to regulate the secretion of hormones by endocrine cells inside of the pituitary and to be a source of growth factors such as basic fibroblast growth factor (bFGF), vascular endothelial growth factors (VEGF), as well as, cytokines as leukaemia inhibitor factor (LIF) and interleukin-6 (IL-6). Functionally, it was suggested that FS cells are capable of initiating immune responses and act as part of a neuroendocrine immune regulation system. Understanding of the way macrophages and/others cells respond to endotoxins and development of innate immunity, a major step was archived with the discovery of Toll-like receptors (TLRs). Toll receptors are members of a membrane-anchored proteins that upon stimulation recruits proteins kinases via a adaptor MyD88 inducing the activation of nuclear factor κB (NF-κB). Recently, nucleotide-binding oligomerization domain (NOD) proteins, NOD1 and NOD2 were found to represent an intracellular pathogen sensing system identified in both immune and non-immune cell types. The ligand of NOD2 is muramyl dipeptide (MDP), a component of bacterial cell-wall peptidoglycan present in most bacterial species. NOD2 oligomerization after bind in MDP activates RICK, an effector molecule that leads to phosphorylation of IKB and release of NF-κB for translocation in the nucleus. Considering characteristics of FS cells and the function of NOD molecules, we decided to investigate the expression and function of NOD in FS cells. Our preliminary RT-PCR data demonstrated the presence of NOD1 and NOD2 transcripts in FS cells. Moreover, NOD2 protein expression was increased in FS cells after 24 hours stimulation with MDP. We also observed significantly enhanced IL-6 secretion in the supernatant of FS cell cultures after stimulation with MDP. The MDP-induced and NOD-mediated IL-6 secretion by FS cells may play a role in modulating hormone secretion (e.g. stimulation of ACTH) during bacterial infections.