IL-1 Receptor Antagonist Protects the Osteogenesis Capability of Gingival-Derived Stem/Progenitor Cells under Inflammatory Microenvironment Induced by Porphyromonas gingivalis Lipopolysaccharides.
IL-1 Receptor Antagonist Protects the Osteogenesis Capability of Gingival-Derived Stem/Progenitor Cells under Inflammatory Microenvironment Induced by Porphyromonas gingivalis Lipopolysaccharides.
复制标题
IL-1受体拮抗剂保护牙龈卟啉单胞菌脂多糖诱导的炎症微环境下牙龈干细胞/祖细胞的成骨能力
DOI：
10.1155/2021/6638575
复制
发表时间：
2021
影响因子：
4.3
通讯作者：
Si M
中科院分区：
文献类型：
--
作者：
Zhao Y;Cai B;Zhu W;Shi J;Wang Y;Si M
间充质干细胞（MSCs）因其良好的再生能力而被认为是牙周炎未来的治疗选择。然而，在局部炎症环境中，如何保护MSCs的生物学特性免受多种细菌毒素的影响仍然是一个挑战。本研究旨在探讨白细胞介素-1受体拮抗剂（IL-1 ra）对牙龈卟啉单胞菌脂多糖（P. gingivalis lipopolysaccharides，LPS）诱导的炎症微环境下牙龈间充质干细胞（gingival-derived mesenchymal stem cells，GMSCs）增殖、迁移和成骨分化的影响。用牙龈卟啉单胞菌-LPS（10 μg/mL）处理来源于SD大鼠游离牙龈组织的GMSC以产生体外炎症环境。用不同浓度的IL-1 ra（0.01 ~ 1 μg/mL）拮抗LPS的负性作用。通过检测细胞增殖、克隆形成单位（CFU）、迁移、成骨分化、矿物质沉积和细胞因子产生等细胞行为，探讨IL-1 ra对炎症状态下GMSCs的保护作用。采用实时定量聚合酶链反应（RT-PCR）和western blot检测LPS对Toll样受体4（TLR 4）/核因子κ B（NF-κB）通路的激活作用。牙龈卟啉单胞菌-LPS处理后，细胞数量、克隆形成率、细胞迁移率、促炎细胞因子产生、成骨分化相关蛋白/mRNA表达以及矿化结节以时间依赖性方式受到抑制。这些负面影响被有效地减弱IL-1 ra管理在时间和剂量依赖性的方式。LPS诱导培养液中加入IL-1 ra后，TLR 4和IkBα的mRNA表达明显降低。Western blot结果显示IL-1 ra可逆转LPS诱导的TLR 4/NF-κB活化。本研究表明IL-1 ra可降低牙龈卟啉单胞菌-LPS诱导的炎症环境中GMSCs上清中炎性细胞因子的产生，从而保护GMSCs的成骨能力和其他生物学特性。这可能与IL-1 ra下调TLR 4介导的NF-κB信号通路激活有关。
Mesenchymal stem cells (MSCs) have been considered to be a future treatment option for periodontitis due to their excellent regenerative capability. However, it is still a challenge to protect MSCs' biological properties from multiple bacterial toxins in local inflammatory environment. The present study is aimed at investigating the treatment effect of interleukin-1 receptor antagonist (IL-1ra) on cell proliferation, migration, and osteogenic differentiation of gingival-derived mesenchymal stem cells (GMSCs) under an inflammatory microenvironment induced by Porphyromonas gingivalis lipopolysaccharides (P. gingivalis-LPS). GMSCs derived from Sprague-Dawley (SD) rats' free gingival tissues were treated with P. gingivalis-LPS (10 μg/mL) to create in vitro inflammatory environment. Different concentrations of IL-1ra (0.01-1 μg/mL) were used to antagonize the negative effect of LPS. Cell behaviors including proliferation, cloning formation unit (CFU), cell migration, osteogenic differentiation, mineral deposition, and cytokine production were assessed to investigate the protection effect of IL-1ra on GMSCs under inflammation. The toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) pathway activated by LPS was evaluated by real-time quantitative polymerase chain reaction (RT-PCR) and western blot. In response to P. gingivalis-LPS treatment, cell numbers, cloning formation rate, cell migration rate, proinflammatory cytokine production, and osteogenic differentiation-associated protein/mRNA expressions as well as mineralized nodules were suppressed in a time-dependent manner. These negative effects were effectively attenuated by IL-1ra administration in a time- and dose-dependent manner. In addition, mRNA expressions of TLR4 and IkBα decreased dramatically when IL-1ra was added into LPS-induced medium. IL-1ra also reversed the LPS-induced TLR4/NF-κB activation as indicated by western blot. The present study revealed that IL-1ra decreased inflammatory cytokine production in a supernatant, so as to protect GMSCs' osteogenesis capacity and other biological properties under P. gingivalis-LPS-induced inflammatory environment. This might be explained by IL-1ra downregulating TLR4-mediated NF-κB signaling pathway activation.
登录
查看更多内容
DOI：
10.4049/jimmunol.0902318
发表时间：
2009-12-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Zhang Q;Shi S;Liu Y;Uyanne J;Shi Y;Shi S;Le AD
通讯作者：
Le AD
影响因子：
3.7
作者：
Akash, Muhammad Sajid Hamid;Rehman, Kanwal;Chen, Shuqing
通讯作者：
Chen, Shuqing
影响因子：
7.5
作者：
Li C;Li B;Dong Z;Gao L;He X;Liao L;Hu C;Wang Q;Jin Y
通讯作者：
Jin Y
DOI：
10.1016/j.bbrc.2010.01.126
发表时间：
2010-03-12
影响因子：
3.1
作者：
Tomar, Geetanjali B.;Srivastava, Rupesh K.;Wani, Mohan R.
通讯作者：
Wani, Mohan R.
生物活性分子在干细胞牙周再生中的贡献。
影响因子：
5.6
作者：
Liu AQ;Hu CH;Jin F;Zhang LS;Xuan K
通讯作者：
Xuan K