Interleukin 19 suppresses RANKL-induced osteoclastogenesis via the inhibition of NF-κB and p38MAPK activation and c-Fos expression in RAW264.7 cells

Abstract

Interleukin 19 (IL-19) is a member of the IL-10 family of cytokines and is known as an inhibitory cytokine. IL-10, also an inhibitory cytokine, suppresses the receptor activator of nuclear factor κB (NF-κB) ligand (RANKL)-induced osteoclast differentiation. However, the effects of IL-19 on osteoclast differentiation are not currently well-understood. In this study, we examined whether IL-19 suppresses osteoclast differentiation in the mouse macrophage-like cell line RAW264.7. We found that IL-19 inhibited RANKL-induced osteoclast differentiation. In addition, IL-19 suppressed RANKL-induced NF-κB and p38 mitogen-activated protein kinase (p38MAPK) activation and c-Fos expression. Moreover, RANKL inhibited IL-19 mRNA expression and secretion in RAW264.7 cells, and the inhibition of the IL-19 function promoted osteoclast differentiation. These results indicate that IL-19 suppressed osteoclast differentiation via the inhibition of NF-κB and p38MAPK activation and c-Fos expression. Furthermore, IL-19 may maintain the osteoclast precursor state, such as monocytes and macrophages. These findings may be useful in the development of osteoclast inhibitors, thereby improving treatments for osteoclast activation-related diseases, such as osteoporosis.

Keywords: Interleukin 19; NF-κB; Osteoclast differentiation; c-Fos; p38MAPK.