Luzza F, Parrello T, Monteleone G, Sebkova L, Romano M, Zarrilli R, Imeneo M, Pallone F
Dipartimento di Medicina Sperimentale e Clinica, Università di Catanzaro Magna Graecia, Catanzaro, Italy.
J Immunol. 2000 Nov 1;165(9):5332-7. doi: 10.4049/jimmunol.165.9.5332.
Helicobacter pylori (HP)-associated gastritis is characterized by an increased number of acute and chronic inflammatory cells secreting cytokines that contribute to maintain and expand the local inflammation. Locally induced IL-8 is believed to play a major role in the HP-associated acute inflammatory response. Factors/mechanisms that regulate IL-8 induction are, however, not fully understood. In the present study we investigated whether HP infection is associated with an increased production of IL-17, a T cell-derived cytokine capable of modulating IL-8 gene expression. We showed that both IL-17 RNA transcripts and protein were expressed at a higher level in the whole gastric mucosal and lamina propria mononuclear cell samples from HP-infected patients than in those from uninfected subjects. HP: eradication was associated with a marked down-regulation of IL-17 expression. The addition of a neutralizing anti-IL-17 Ab to the gastric lamina propria mononuclear cell cultures resulted in a significant inhibition of IL-8 secretion, indicating that IL-17 contributes to enhance IL-8 in the HP-colonized gastric mucosa. Consistently, stimulation of MKN 28 cells, a gastric epithelial cell line, with IL-17 increased IL-8 secretion. Finally, conditioned medium from the IL-17-stimulated MKN 28 cell cultures promoted the in vitro polymorphonuclear leukocyte migration. This effect was inhibitable by a neutralizing IL-8 but not IL-17 Ab. Together, these data indicate that biologically active IL-17 production is increased during HP: infection, suggesting the possibility that this cytokine may play an important role in the inflammatory response to the HP colonization.
幽门螺杆菌（HP）相关性胃炎的特征是分泌细胞因子的急性和慢性炎症细胞数量增加，这些细胞因子有助于维持和扩大局部炎症。局部诱导的白细胞介素-8（IL-8）被认为在HP相关性急性炎症反应中起主要作用。然而，调节IL-8诱导的因素/机制尚未完全了解。在本研究中，我们调查了HP感染是否与IL-17产生增加有关，IL-17是一种能够调节IL-8基因表达的T细胞衍生细胞因子。我们发现，与未感染受试者相比，HP感染患者的全胃黏膜和固有层单核细胞样本中IL-17 RNA转录本和蛋白质的表达水平更高。HP根除与IL-17表达的显著下调有关。向胃固有层单核细胞培养物中添加中和性抗IL-17抗体可显著抑制IL-8分泌，表明IL-17有助于增强HP定植胃黏膜中的IL-8。同样，用IL-17刺激胃上皮细胞系MKN 28细胞可增加IL-8分泌。最后，IL-17刺激的MKN 28细胞培养物的条件培养基促进了体外多形核白细胞迁移。这种作用可被中和性IL-8抗体抑制，但不能被IL-17抗体抑制。总之，这些数据表明，在HP感染期间生物活性IL-17的产生增加，提示这种细胞因子可能在对HP定植的炎症反应中起重要作用。
