Enhancement of gingival inflammation induced by synergism of IL-1β and IL-6
Enhancement of gingival inflammation induced by synergism of IL-1β and IL-6
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DOI：
10.2220/biomedres.34.31
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发表时间：
2013-02-01
影响因子：
1.2
通讯作者：
Naruishi, Koji
中科院分区：
文献类型：
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作者：
Sawada, Shunsuke;Chosa, Naoyuki;Naruishi, Koji
白细胞介素-1（IL-1）和IL-6是参与牙周炎等炎症性疾病的最有效的促炎细胞因子。本研究的目的是通过靶向培养的人牙龈成纤维细胞（HGFs）来检测IL-1 β和IL-6对牙龈炎症的协同作用。用IL-1 β或IL-6/可溶性IL-6 R（sIL-6 R）处理HGF，收集总RNA和总细胞裂解物，以使用qRT-PCR和Western印迹法检查已知为IL-6的信号转导子的gp 130的表达。使用ELISA方法检测HGF中IL-1 β介导的IL-6生产率。同样，在用IL-1 β、TNF-α和IL-6处理HGF和THP-1巨噬细胞后，检测sIL-6 R的产生。然后，在IL-1 β预处理后，用IL-6/sIL-6 R处理HGF，并使用Western印迹检测细胞内信号。最后，使用qRT-PCR和ELISA方法检测IL-1 β预处理后用IL-6/sIL-6 R处理的HGF中各种mRNA/蛋白质的表达。IL-1 β显著增加HGF中gp 130和IL-6的表达。IL-6显著增加THP-1巨噬细胞sIL-6 R的产生，但对HGF无明显影响。IL-1 β和IL-6/sIL-6 R共刺激可显著诱导HGF中Stat 3、ERK和INK的磷酸化。有趣的是，多种炎症相关分子如MMP-1，MCP-1，IL-1 ra，bFGF和VEGF的表达通过与IL-1 β和IL-6/sIL-6 R共刺激而增强。牙龈炎症受IL-1 β和IL-6/sIL-6 R协同作用的HGF调节，通过诱导gp 130表达，导致牙周炎的进展。
Internleukin-1 (IL-1) and IL-6 are the most potent proinflammatory cytokines being involved in inflammatory diseases such as periodontitis. The objective of this study was to examine the synergistic effects of IL-1 beta and IL-6 on gingival inflammation by targeting cultured human gingival fibroblasts (HGFs). HGFs were treated with IL-1 beta or IL-6/soluble IL-6R (sIL-6R), and total RNA and total cell lysate were collected to examine expression of gp130 known as a signal transducer of IL-6 using qRT-PCR and Western blotting. IL-1 beta-mediated IL-6 productivity in HGFs was examined using ELISA method. Likewise, after HGFs and THP-1 macrophages were treated with IL-1 beta, TNF-alpha and IL-6, sIL-6R productivity was examined. Next, HGFs were treated with IL-6/sIL-6R after pretreatment of IL-1 beta, and the intracellular signals were examined using Western blotting Finally, various mRNA/protein expressions in HGFs treated with IL-6/sIL-6R after pretreatment of IL-1 beta were examined using qRT-PCR and ELISA method. IL-1 beta increased significantly both gp130 and IL-6 expression in HGFs. IL-6 increased significantly sIL-6R production in THP-1 macrophages but not HGFs. Co-stimulation with IL-1 beta and IL-6/sIL-6R induced dramatically the phosphorylation of Stat3, ERK and INK in HGFs. Interestingly, expression of various inflammation-related molecules such as MMP-1, MCP-1, IL-1ra, bFGF and VEGF were enhanced by co-stimulation with IL-1 beta and IL-6/sIL-6R in HGFs. Gingival inflammation is regulated by HGFs affected by both IL-1 beta and IL-6/sIL-6R synergistically through induction of gp130 expression, resulting in progression of periodontitis.