Investigation of Interleukin 1B synthesis and secretion by dendritic cells: Interplay between toll-like receptor and FCG receptor

Abstract

Interleukin-1I? (IL-1I?) is a prototypic multifunctional cytokine. It not only mediates inflammatory response in innate immunity, but also modulates antigen-specific immunity. Dendritic cells (DCs) are central regulator of immune activation and tolerance. However, the regulation of IL-1I? production in DCs is less clear. In this project, the underlying regulatory mechanisms of IL-1I? synthesis and secretion in monocyte-derived DCs (moDCs) are investigated. It was observed that, LPS stimulation induced moDCs to express IL-1I? mRNA, synthesize pro-IL-1I? and process IL-1I?i? precursors, but with little mature IL-1I? secretion; immobilized IgG (imIgG) stimulation induced little IL-1I? mRNA expression and protein synthesis by moDCs. However, co-stimulation with LPS and imIgG resulted in dramatic increase in IL-1I? secretion from moDCs. The increase was mediated through P2X7 receptor-dependent Ca2+ influx. In addition, Rac1, JNK and MEK were identified as key molecules in LPS/imIgG-induced IL-1I? production and secretion by moDCs, whilst PI3-K and p38 MAPK as negative modulators.