کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2779407 1153272 2012 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
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
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شناسی تکاملی
پیش نمایش صفحه اول مقاله
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
چکیده انگلیسی

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


► IL-4 significantly inhibited TNF-α induced osteoclastogenesis in vivo.
► IL-4 inhibited TNF-α-induced RANKL mRNA expression in vitro and in vivo.
► IL-4 affects both stromal cells and osteoclast precursors in TNF-α-mediated oeteoclastogenesis in vivo.
► IL-4 also inhibited TNF-α-induced osteoclastogenesis in mice blocked T cell.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bone - Volume 51, Issue 4, October 2012, Pages 771–780
نویسندگان
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