Endothelin-1 induces interleukin-18 expression in human osteoblasts

Area of Science:

• Bone biology
• Cell signaling
• Endocrinology

Background:

• Endothelin-1 (ET-1) and interleukin-18 (IL-18) are known to promote osteoblast proliferation.
• The interaction between ET-1 and IL-18 in osteoblasts has not been previously investigated.

Purpose of the Study:

• To investigate the effect of ET-1 on IL-18 expression in cultured human osteoblasts.
• To elucidate the signaling pathways involved in ET-1-mediated IL-18 induction.
• To determine the role of IL-18 in ET-1-induced osteoblast proliferation.

Main Methods:

• Human osteoblasts were treated with varying concentrations and durations of ET-1.
• ET A receptor (ETAR) and ET B receptor (ETBR) blockers, p38 MAPK siRNA, and kinase inhibitors were used.
• Gene promoter activity, mRNA, and protein expression of IL-18 were measured.
• Osteoblast proliferation was assessed using [(3)H]thymidine incorporation assays.
• Endogenous IL-18 expression was knocked down to evaluate its role in ET-1's effects.

Main Results:

• ET-1 significantly increased IL-18 mRNA and protein expression in a dose- and time-dependent manner.
• The promoting effect of ET-1 on IL-18 expression was abolished by ETAR blockade and p38 MAPK inhibition.
• Knocking down endogenous IL-18 significantly reduced ET-1's effect on osteoblast proliferation (by 57%).

Conclusions:

• ET-1 induces IL-18 expression in human osteoblasts via ETAR and a p38 MAPK-dependent pathway.
• IL-18 plays a crucial role in mediating ET-1-induced osteoblast proliferation.
• This study reveals a novel interaction between ET-1 and IL-18, offering new insights into bone physiology and pathophysiology.