Physiopathology of Inflammatory Bone Diseases, EA2603, University Lille North of France, Quai Masset, Bassin Napoléon BP120, 62327 Boulogne/Mer, France.
Cytokine. 2011 Mar;53(3):347-54. doi: 10.1016/j.cyto.2010.11.021. Epub 2010 Dec 28.
The aim of the present study was to investigate the potential role of the recently discovered IL-1 family member IL-33 in bone remodeling. Our results indicate that IL-33 mRNA is expressed in osteocytes in non-inflammatory human bone. Moreover, IL-33 levels are increased by TNF-α and IL-1β in human bone marrow stromal cells, osteoblasts and adipocytes obtained from three healthy donors. Experiments with the inhibitor GW-9662 suggested that expression of IL-33, in contrast to that of IL-1β, is not repressed by PPARγ likely explaining why IL-33, but not IL-1β, is expressed in adipocytes. The IL-33 receptor ST2L is not constitutively expressed in human bone marrow stromal cells, osteoblasts or CD14-positive monocytes, and IL-33 has no effect on these cells. In addition, although ST2L mRNA is induced by TNF-α and IL-1β in bone marrow stromal cells, IL-33 has the same effects as TNF-α and IL-1β, and, therefore, the biological activity of IL-33 may be redundant in this system. In agreement with this hypothesis, MC3T3-E1 osteoblast-like cells constitutively express ST2L mRNA, and IL-33 and TNF-α/IL-1β similarly decrease osteocalcin RNA levels in these cells. In conclusion, our results suggest that IL-33 has no direct effects on normal bone remodeling.
本研究旨在探讨最近发现的白细胞介素 1 家族成员白细胞介素 33 在骨重塑中的潜在作用。我们的结果表明，白细胞介素 33 mRNA 在非炎症性人骨中的破骨细胞中表达。此外，TNF-α 和 IL-1β 可增加来自 3 名健康供体的人骨髓基质细胞、成骨细胞和脂肪细胞中白细胞介素 33 的水平。用抑制剂 GW-9662 进行的实验表明，与白细胞介素 1β 相反，白细胞介素 33 的表达不受 PPARγ 抑制，这可能解释了为什么白细胞介素 33 而不是白细胞介素 1β 在脂肪细胞中表达。IL-33 受体 ST2L 在人骨髓基质细胞、成骨细胞或 CD14 阳性单核细胞中不持续表达，IL-33 对这些细胞没有影响。此外，尽管 TNF-α 和 IL-1β 可诱导骨髓基质细胞中 ST2L mRNA 的表达，但白细胞介素 33 具有与 TNF-α 和 IL-1β 相同的作用，因此，白细胞介素 33 的生物学活性在该系统中可能是多余的。与该假说一致，MC3T3-E1 成骨样细胞持续表达 ST2L mRNA，白细胞介素 33 和 TNF-α/IL-1β 相似地降低这些细胞中骨钙素 RNA 水平。总之，我们的结果表明白细胞介素 33 对正常骨重塑没有直接影响。
