Regulatory Roles of Osteopontin in Production of Monocyte-Origin MCP-1:

Osteopontin (OPN), expressed by various immune cells, plays a critical role in leukocyte migration. Although OPN was found to selectively induce the expression of proinflammatory chemokines, the molecular mechanisms that control OPN gene expression and its underlying mechanism for migration and recruitment of inflammatory cells remain largely unknown. In this study, real-time polymerase chain reaction and enzyme-linked immunosorbent assay were used to determine OPN and monocyte chemoattractant protein 1 (MCP-1) expression. Signaling and molecular events between OPN and MCP-1 were analyzed by Western blot. Leukocyte migration in the presence of OPN was measured by chemotaxis assay. Our data indicated that phosphoinositide 3-kinase (PI3K), c-Jun NH2-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) that are activated upon stimulation with lipopolysaccharide were shown to upregulate OPN expression. Endogenous production of OPN was attributable to increased production of MCP-1, and this e...