Lactoferricin mediates anti-inflammatory and anti-catabolic effects via inhibition of IL-1 and LPS activity in the intervertebral disc.
Lactoferricin mediates anti-inflammatory and anti-catabolic effects via inhibition of IL-1 and LPS activity in the intervertebral disc.
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DOI：
10.1002/jcp.24350
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发表时间：
2013-09
影响因子：
5.6
通讯作者：
Im, Hee-Jeong
中科院分区：
文献类型：
--
作者：
Kim, Jae-Sung;Ellman, Michael B.;Yan, Dongyao;An, Howard S.;Ranjan, K. C.;Li, Xin;Chen, Di;Xiao, Guozhi;Cs-Szabo, Gabriella;Hoskin, David W.;Buechter, Doug D.;Van Wijnen, Andre J.;Im, Hee-Jeong
分解代谢细胞因子白细胞介素-1 (IL-1) 和内毒素脂多糖 (LPS) 是众所周知的参与退行性椎间盘疾病的炎症介质，IL-1 和 LPS 的抑制剂可能可用于减缓或预防体内椎间盘退变。在这里，我们利用体外和离体分析阐明了牛乳铁蛋白 (LfcinB) 通过拮抗 IL-1 和 LPS 介导的分解代谢活性在椎间盘 (IVD) 中具有显着的抗分解代谢和抗炎作用。具体来说，我们在使用牛和人髓核 (NP) 细胞的长期（藻酸盐珠）和短期（单层）培养模型中证明了 LfcinB 对 IL-1 和 LPS 介导的蛋白聚糖 (PG) 消耗、基质降解酶产生和酶活性的生物抵消作用。 LfcinB 显着减弱 IL-1 和 LPS 介导的 PG 产生和合成抑制，从而恢复 PG 积累和细胞周基质形成。同时，LfcinB 在牛 NP 细胞中在 mRNA 和蛋白质水平上拮抗分解代谢因子介导的多种软骨降解酶的诱导，包括 MMP-1、MMP-3、MMP-13、ADAMTS-4 和 ADAMTS-5。 LfcinB 还抑制分解代谢因子诱导的氧化和炎症因子的刺激，例如 iNOS、IL-6、Toll 样受体 2 (TLR-2) 和 TLR-4。最后，LfcinB 拮抗 IL-1 和 LPS 介导的 PG 抑制的能力在整体椎间盘内显微注射模型中得到证实，随后使用小鼠和兔 IVD 组织进行离体器官培养，这表明 LfcinB 在未来对退行性椎间盘疾病具有潜在的治疗益处。
The catabolic cytokine interleukin-1 (IL-1) and endotoxin lipopolysaccharide (LPS) are well-known inflammatory mediators involved in degenerative disc disease, and inhibitors of IL-1 and LPS may potentially be used to slow or prevent disc degeneration in vivo. Here, we elucidate the striking anti-catabolic and anti-inflammatory effects of bovine lactoferricin (LfcinB) in the intervertebral disc (IVD) via antagonism of both IL-1 and LPS-mediated catabolic activity using in vitro and ex vivo analyses. Specifically, we demonstrate the biological counteraction of LfcinB against IL-1 and LPS-mediated proteoglycan (PG) depletion, matrix-degrading enzyme production and enzyme activity in long-term (alginate beads) and short-term (monolayer) culture models using bovine and human nucleus pulposus (NP) cells. LfcinB significantly attenuates the IL-1 and LPS-mediated suppression of PG production and synthesis, and thus restores PG accumulation and pericellular matrix formation. Simultaneously, LfcinB antagonizes catabolic factor mediated induction of multiple cartilage-degrading enzymes, including MMP-1, MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5, in bovine NP cells at both mRNA and protein levels. LfcinB also suppresses the catabolic factor-induced stimulation of oxidative and inflammatory factors such as iNOS, IL-6, and toll-like receptor-2 (TLR-2) and TLR-4. Finally, the ability of LfcinB to antagonize IL-1 and LPS-mediated suppression of PG is upheld in an en bloc intradiscal microinjection model followed by ex vivo organ culture using both mouse and rabbit IVD tissue, suggesting a potential therapeutic benefit of LfcinB on degenerative disc disease in the future.
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影响因子：
3.6
作者：
Aota, Yoichi;An, Howard S.;Masuda, Koichi
通讯作者：
Masuda, Koichi
影响因子：
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作者：
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影响因子：
3
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通讯作者：
Masuda, K
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作者：
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通讯作者：
Hanci, Murat
影响因子：
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作者：
Hayashida, K;Kaneko, T;Harada, E
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Harada, E