Folliculostellate (FS) cells were found to regulate hormonal secretion in pituitary endocrine cells. This cell type share properties with components of the innate immune response such as dendritic cells and macrophages, and it is suggested that they are able to initiate immune responses and act as part of an immunoendocrine regulation system. Members of toll-like receptor (TLR) family recognize bacterial cell wall components and initiate an immune response. Recently, we detected by RT-PCR the TLR4 mRNA expression in FS cell line, TtT/GF. In the present study, we detected the constitutive expression of two members of a novel nucleotide-binding oligomerization domain (NOD) family of proteins that act as cytosolic receptors. We show that NOD1 and NOD2 are expressed in the human and mouse pituitary glands, and in TtT/GF cells. Furthermore, NOD1-agonistic diaminopimelic acid (DAP) and NOD2-agonistic muramyl dipeptide (MDP) induced (NF)-κB activation and ERK1/2 phosphorylation in TtT/GF cell cultures. Both NOD agonists in combination with TLR4 agonistic, LPS enhanced NF-κB transcriptional activity, and interleukin-6 (IL-6) production in these cells. Knocking-down NOD1 and NOD2 markedly inhibited LPS induced IL-6 production in TtT/GF cells. RNA interference for NOD2, but not NOD1, downregulated NF-κB activity. LPS, MDP and LPS plus MDP increased NF-κB expression and transcriptional activity, in a mechanism involving STAT3, since knocking-down this protein abolished NF-κB activation. All together, we revealed that NOD1 and NOD2 expression expressed in TtT/GF where they mediate LPS signals in these cells. Finally, these findings suggest that FS cells play a predominant role in the context of immune-endocrine interactions during bacterial infection and inflammation and NOD proteins have a central participation in these processes.
03 - 07 May 2008
European Society of Endocrinology