EPITHELIAL-CELLS SECRETE THE CHEMOKINE INTERLEUKIN-8 IN RESPONSE TO BACTERIAL ENTRY
EPITHELIAL-CELLS SECRETE THE CHEMOKINE INTERLEUKIN-8 IN RESPONSE TO BACTERIAL ENTRY
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DOI：
10.1128/iai.61.11.4569-4574.1993
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发表时间：
1993-11-01
影响因子：
3.1
通讯作者：
FIERER, J
中科院分区：
文献类型：
--
作者：
ECKMANN, L;KAGNOFF, MF;FIERER, J
粘膜表面的细菌侵入导致多形核白细胞的快速流入。负责这种反应的趋化刺激尚不清楚。由于上皮细胞是许多肠道病原体进入的第一批细胞之一，我们研究了上皮细胞通过释放趋化细胞因子为粘膜炎症反应提供早期信号的能力。如本文所示，趋化因子白细胞介素-8（IL-8），一种有效的多形核白细胞的化学引诱物和激活剂，由肠和宫颈上皮细胞响应细菌进入而分泌。此外，各种不同的细菌，包括那些留在吞噬体空泡内的细菌，沙门氏菌属，以及那些进入细胞质的，例如，单核细胞增生李斯特菌刺激了这种反应。感染后90 min内可检测到IL-8 mRNA水平升高。无论是细菌脂多糖，也不是非侵入性细菌，包括大肠杆菌和屎肠球菌，诱导IL-8的反应。此外，已知由一些上皮细胞表达的肿瘤坏死因子α在细菌进入后的培养上清液中未检测到，并且加入抗肿瘤坏死因子α抗体对细菌进入后的IL-8应答没有影响。这些数据提示了新的概念，即上皮细胞作为细菌进入后宿主免疫和炎症细胞在下层粘膜中的早期信号系统。
Bacterial invasion of mucosal surfaces results in a rapid influx of polymorphonuclear leukocytes. The chemotactic stimulus responsible for this response is not known. Since epithelial cells are among the first cells entered by many enteric pathogens, we investigated the ability of epithelial cells to provide an early signal for the mucosal inflammatory response through the release of chemotactic cytokines. As shown herein, the chemokine interleukin-8 (IL-8), a potent chemoattractant and activator of polymorphonuclear leukocytes, was secreted by intestinal and cervical epithelial cells in response to bacterial entry. Moreover, a variety of different bacteria, including those that remain inside phagosomal vacuoles, e.g., Salmonella spp., and those that enter the cytoplasm, e.g., Listeria monocytogenes, stimulated this response. Increased IL-8 mRNA levels could be detected within 90 min after infection. Neither bacterial lipopolysaccharide nor noninvasive bacteria, including Escherichia coli and Enterococcus faecium, induced an IL-8 response. Moreover, tumor necrosis factor alpha, which is known to be expressed by some epithelial cells, was not detected in the culture supernatants after bacterial entry, and addition of anti-tumor necrosis factor alpha antibodies had no effect on the IL-8 response following bacterial entry. These data suggest the novel concept that epithelial cells serve as an early signaling system to host immune and inflammatory cells in the underlying mucosa following bacterial entry.