Bacterial phospholipase C upregulates matrix metalloproteinase expression by cultured epithelial cells
Bacterial phospholipase C upregulates matrix metalloproteinase expression by cultured epithelial cells
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细菌磷脂酶 C 上调培养上皮细胞的基质金属蛋白酶表达
DOI：
10.1128/iai.65.12.4931-4936.1997
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发表时间：
1997
影响因子：
3.1
通讯作者：
V. Uitto
中科院分区：
文献类型：
--
作者：
J. Firth;E. Putnins;Hannu Larjava;V. Uitto
磷脂酶C（PLC）是多种病原菌的公认毒力因子。我们研究了外源性PLC是否会扰乱感染组织中的上皮行为。细胞培养基的明胶和酪蛋白酶谱表明，蜡样芽孢杆菌的广谱PLC诱导人皮肤上皮细胞（NHEK）、人牙龈上皮细胞（HGE）和猪牙周膜上皮细胞（PLE）产生基质金属蛋白酶（MMP）。在所有三种细胞类型中，MMP-9（92 kDa明胶酶）活性在0.1 U/ml时增加最强（9倍），并且在0.1至1.0 U/ml范围内，该效应呈剂量依赖性。在每种细胞类型中也观察到MMP-2（72-kDa明胶酶）相对较弱的增加（两倍）。MMP-3（48-kDa基质溶解素）的PLC诱导也见于明胶上的NHEK和HGE中，并且通过酪蛋白酶谱法对PLE更敏感（五倍）。通过14 C标记的变性I型胶原的降解测量的总明胶分解活性增加了约18倍（NHEK）、12倍（HGE）和14倍（PLE）。北方分析显示MMP-9明显增加，MMP-3 mRNA水平略有增加，但MMP-2 mRNA水平无显著增加。进一步的研究显示，在没有血清的情况下，PLC对MMP-9的诱导随着细胞培养时间的延长而逐渐增加。PLC对MMP的诱导是极性的，MMP-9和MMP-3主要在顶端方向分泌，MMP-2主要在基底方向分泌。磷脂酰肌醇信号通路的抑制剂新霉素可阻断PLC的作用。没有观察到显着的影响，在MMP的表达与钙离子载体A23187或磷脂酶A2。形态学上，PLC处理导致培养细胞之间的接触减少和细胞表面微绒毛的损失。这些结果表明，PLC分泌的细菌病原体可能会破坏感染组织的上皮细胞，并通过诱导MMPs增加上皮下组织的破坏。
Phospholipase C (PLC) is a putative virulence factor of several pathogenic bacteria. We studied if exogenous PLC would perturb epithelial behavior in infected tissues. Gelatin and casein zymography of cell culture medium indicated that the broad-spectrum PLC of Bacillus cereus induced matrix metalloproteinase (MMP) production in epithelial cells of human skin (NHEK), human gingiva (HGE), and porcine periodontal ligament (PLE). In all three cell types, the strongest increase (ninefold) at 0.1 U/ml was seen in the MMP-9 (92-kDa gelatinase) activity, and the effect was dose dependent in the range of 0.1 to 1.0 U/ml. A relatively weaker increase (twofold) in MMP-2 (72-kDa gelatinase) was also observed in each cell type. PLC induction of MMP-3 (48-kDa stromelysin) was also seen in NHEK and HGE on gelatin and more sensitively for PLE by casein zymography (fivefold). Total gelatinolytic activity as measured by degradation of 14C-labeled denatured type I collagen increased by about 18-fold (NHEK), 12-fold (HGE), and 14-fold (PLE). Northern analysis showed a clear increase in the MMP-9, and a minor increase in MMP-3 mRNA levels but no significant increase in MMP-2 mRNA levels. Further studies with PLE revealed that MMP-9 induction by PLC progressively increased with the length of cell culture time in the absence of serum. PLC induction of MMPs was polar, with MMP-9 and MMP-3 secreted primarily in the apical direction and MMP-2 secreted mainly in the basal direction. The PLC effect was blocked by neomycin, an inhibitor of the phosphoinositol signal pathway. No significant effects were observed in MMP expression with the calcium ionophore A23187 or phospholipase A2. Morphologically, PLC treatment resulted in reduced contacts between the cultured cells and loss of the cell surface microvilli. These results suggest that PLC secreted by bacterial pathogens may disrupt epithelium of infected tissue and increase the subepithelial tissue destruction through induction of MMPs.
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DOI：
10.1172/jci116073
发表时间：
1992-11
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
U. K. Saarialho-Kere;E. S. Chang;H. Welgus;William C. Parks
通讯作者：
U. K. Saarialho-Kere;E. S. Chang;H. Welgus;William C. Parks
I 型胶原增强了 92 kDa 角质细胞衍生的 IV 型胶原酶的组成型合成，而 IV 型胶原基质则减少了这种合成。
DOI：
10.1111/1523-1747.ep12614800
发表时间：
1992
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
Sarret,Y;Woodley,DT;Goldberg,GS;Kronberger,A;Wynn,KC
通讯作者：
Wynn,KC
暴露于细菌内毒素的人单核细胞样细胞中间质胶原酶和 92-kDa 明胶酶表达的不同机制调节。
DOI：
--
发表时间：
1993
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Saarialho-Kere,UK;Welgus,HG;Parks,WC
通讯作者：
Parks,WC
影响因子：
7.5
作者：
Spiegel, S;Foster, D;Kolesnick, R
通讯作者：
Kolesnick, R