IL-4 inhibits TNF-α-mediated osteoclast formation by inhibition of RANKL expression in TNF-α-activated stromal cells and direct inhibition of TNF-α-activated osteoclast precursors via a T-cell-independent mechanism in vivo.

摘要: It has been reported that osteoclastogenesis is induced by tumor necrosis factor (TNF)-α. Interleukin (IL)-4 the most important cytokine involved in humoral immunity. However, no studies have investigated effect of IL-4 on TNF-α-mediated osteoclast formation vivo. In this study, we TNF-α was administered with and without into supracalvariae mice. The number osteoclasts levels mRNA for cathepsin K tartrate-resistant acid phosphate, both markers, mice were lower than those alone. level phosphatase form 5b (TRACP5b) as a marker bone resorption also lower. We showed inhibited precursors vitro. Expression receptor activator NF-κB ligand (RANKL) TNF-α-activated stromal cells inhibited. Furthermore, whether had effects Using whose chimeric presence TNF receptors, TNF-α-responsive cells, TNF-α-induced RANKL expression This event dependent p38 inhibition Additionally, T cell-depleted summary, conclude inhibiting directly vivo via cell-independent mechanism.