Force-induced IL-8 from Periodontal Ligament Cells Requires IL-1β

Abstract

During orthodontic tooth movement, mechanical stresses induce inflammatory reactions in the periodontal ligament (PDL). We hypothesized that chemokines released from PDL cells under mechanical stress regulate osteoclastogenesis, and investigated the profiles and mechanisms of chemokine expression by human PDL cells in response to mechanical stress. In vitro, shear stress and pressure force rapidly increased the gene and protein expressions of IL-8/CXCL8 by PDL cells. Consistently, amounts of IL-8 in the gingival crevicular fluid of healthy individuals increased within 2 to 4 days of orthodontic force application. The PDL cells constitutively expressed low levels of IL-1beta, which were not further increased by mechanical stress. Interestingly, neutralization of IL-1beta abolished IL-8 induction by mechanical stresses, indicating that IL-1beta is essential for IL-8 induction, presumably though autocrine or paracrine mechanisms. Finally, experiments with signal-specific inhibitors indicated that MAP kinase activation is essential for IL-8 induction.

Roles of Kinases in Osteoblast Function

“…On the other hand, transient activation of p38 kinase in osteoblasts has been reported to be induced by cyclic stretch (Kusumi et al 2005), compression (Maeda et al 2007), fluid shear stress (Lee et al 2008;Yeh et al 2010), and magnetic force (Yuge et al 2003). Recent reports indicated that p38 activation is essential for Opg expression induced by cyclic stretch (Kusumi et al 2005), and compression-induce IL-8 expression (Maeda et al 2007). Intriguingly, acceleration of osteoblast differentiation induced by magnetic force is mainly attributed to p38 kinase activation, while the activity of ERKs or JNKs is dispensable (Yuge et al 2003).…”

“…Transient activation of JNKs in osteoblasts has been reported to be induced by cyclic stretch (Danciu et al 2003), compression (Maeda et al 2007), and fluid shear stress (Lee et al 2008;. It has been reported that JNK activity is important for compressioninduced IL-8 expression (Maeda et al 2007).…”

“…Mechanical stresses have been reported to be associated with increased proliferation, accelerated differentiation, and inhibition of apoptosis of osteoblasts (Aguirre et al 2006;Robling and Turner 2009;Turner et al 2009). Recent lines of evidence have also revealed that mechanical stresses induce the expression of RANKL, inflammatory cytokines, and chemokines by osteoblasts Maeda et al 2007). However, the reception and intracellular signals transducing these stresses (termed as mechanotransduction) of osteoblasts are not well understood.…”

“…It has been reported that JNK activity is important for compressioninduced IL-8 expression (Maeda et al 2007). On the other hand, transient activation of p38 kinase in osteoblasts has been reported to be induced by cyclic stretch (Kusumi et al 2005), compression (Maeda et al 2007), fluid shear stress (Lee et al 2008;Yeh et al 2010), and magnetic force (Yuge et al 2003). Recent reports indicated that p38 activation is essential for Opg expression induced by cyclic stretch (Kusumi et al 2005), and compression-induce IL-8 expression (Maeda et al 2007).…”

“…However, mechanical stresses often induce tissue inflammation in bones, especially when they are excessive. We and others have recently revealed that osteoblasts respond to mechanical stresses by expressing various inflammatory cytokines and chemokines Maeda et al 2007). …”