HELICOBACTER-PYLORI INDUCED INTERLEUKIN-8 EXPRESSION IN GASTRIC EPITHELIAL-CELLS IS ASSOCIATED WITH CAGA POSITIVE PHENOTYPE
HELICOBACTER-PYLORI INDUCED INTERLEUKIN-8 EXPRESSION IN GASTRIC EPITHELIAL-CELLS IS ASSOCIATED WITH CAGA POSITIVE PHENOTYPE
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DOI：
10.1136/jcp.48.1.41
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发表时间：
1995-01-01
影响因子：
3.4
通讯作者：
RAPPUOLI, R
中科院分区：
文献类型：
--
作者：
CRABTREE, JE;COVACCI, A;RAPPUOLI, R
目的-使用一系列具有不同CagA和VacA的幽门螺杆菌天然表型变异株（空泡细胞毒素）表达，以确定哪些细菌因子与上皮白细胞介素-8（IL-8）诱导更密切相关。（AGS和KATO-3）与5种幽门螺杆菌菌株共培养，所述5种幽门螺杆菌菌株不同地显示出表达cagA基因/CagA蛋白、VacA和/或显示出生物细胞毒性。用酶漏免疫吸附试验（ELISA）测定分泌的IL-8，用逆转录聚合酶链反应（RT-PCR）测定IL-8信使RNA（mRNA）。结果-表达CagA的菌株，包括无细胞毒性且不表达VacA蛋白的变异株（D931），被发现上调上皮细胞IL-8的分泌和基因表达。相反，菌株没有CagA的表达，即使在VacA和/或生物细胞毒性的存在下，（G104，BA 142），未能诱导IL-8蛋白或mRNA以上的控制values.Conclusions -这些结果强烈支持幽门螺杆菌CagA或共表达因子以外的细胞毒素在胃上皮IL-8的上调的作用。除了直接细胞毒性外，上皮细胞IL-8分泌增加和伴随的中性粒细胞趋化性和活化可能是组织损伤和溃疡形成的重要因素。
Aims - To use a range of natural phenotypically variant strains of Helicobacter pylori with disparate CagA and VacA (vacuolating cytotoxin) expression to determine which bacterial factors are more closely associated with epithelial interleukin-8 (IL-8) induction.Methods - Gastric epithelial cells (AGS and KATO-3) were co-cultured with five H pylori strains which were variously shown to express the cagA gene/CagA protein, VacA and/or to exhibit biological cytotoxicity. Secreted IL-8 was assayed by enzyme leaked immunosorbent assay (ELISA) and IL-8 messenger RNA (mRNA) was assayed using a reverse transcription polymerase chain reaction based technique (RT-PCR).Results - Strains expressing CagA, including a variant strain (D931) which is non-cytotoxic and does not express the VacA protein, were found to upregulate epithelial IL-8 secretion and gene expression. In contrast, strains with no CagA expression, even in the presence of VacA and/or biological cytotoxicity, (G104, BA142), failed to induce IL-8 protein or mRNA above control values.Conclusions - These results strongly support a role for H pylori CagA or coexpressed factors other than the cytotoxin in upregulation of gastric epithelial IL-8. Increased epithelial IL-8 secretion and concomitant neutrophil chemotaxis and activation in addition to direct cytotoxicity may be an important factor in tissue damage and ulceration.