白细胞介素-17家族成员在人结肠上皮下肌成纤维细胞中诱导的炎症反应。
Inflammatory responses induced by interleukin-17 family members in human colonic subepithelial myofibroblasts.
作者信息
Yagi Yuhki, Andoh Akira, Inatomi Osamu, Tsujikawa Tomoyuki, Fujiyama Yoshihide
机构信息
Department of Internal Medicine, Shiga University of Medical Science, Seta-Tsukinowa, Otsu, 520-2192, Japan.
出版信息
J Gastroenterol. 2007 Sep;42(9):746-53. doi: 10.1007/s00535-007-2091-3. Epub 2007 Sep 25.
BACKGROUND
We investigated the potential role of interleukin (IL)-17 family members (IL-17A to IL-17F) in the induction of inflammatory responses in human colonic subepithelial myofibroblasts (SEMFs).
METHODS
The expression of the inflammatory cytokines IL-6, IL-8, leukemia inhibitory factor (LIF), and matrix metalloproteinases (MMP)-1 and MMP-3 were evaluated by enzyme-linked immunosorbent assay and Northern blotting. Activation of mitogen-activated protein kinase (MAPK) was assessed by immunoblotting.
RESULTS
IL-17A and IL-17F significantly enhanced IL-6, IL-8, LIF, MMP-1, and MMP-3 secretion. The effects of IL-17A were relatively stronger than those induced by IL-17F. The effects of IL-17B, IL-17C, IL-17D, and IL-17E were modest as compared with those induced by IL-17A and IL-17F. Both IL-17A and IL-17F augmented IL-1beta-induced secretion of IL-6, IL-8, LIF, MMP-1, and MMP-3. A similar augmentation was also observed in tumor necrosis factor (TNF)-alpha-induced cytokine and MMP secretion. IL-17A and IL-17F rapidly induced phosphorylation of extracellular signal-regulated kinases (ERK) 1/2, p38 MAPKs, and c-Jun-NH(2)-terminal kinase (JNK) as early as 15 min after stimulation. Inhibitors for ERK (PD98059 and U0216) and p38 MAPK (SB203580) significantly reduced the IL-17F-induced IL-6, IL-8, LIF, MMP-1, and MMP-3 secretion.
CONCLUSIONS
Among IL-17 family members, IL-17A and IL-17F strongly stimulate human colonic SEMFs, inducing inflammatory responses.
背景
我们研究了白细胞介素（IL）-17家族成员（IL-17A至IL-17F）在人结肠上皮下肌成纤维细胞（SEMFs）炎症反应诱导中的潜在作用。
方法
通过酶联免疫吸附测定和Northern印迹法评估炎性细胞因子IL-6、IL-8、白血病抑制因子（LIF）以及基质金属蛋白酶（MMP）-1和MMP-3的表达。通过免疫印迹法评估丝裂原活化蛋白激酶（MAPK）的激活情况。
结果
IL-17A和IL-17F显著增强IL-6、IL-8、LIF、MMP-1和MMP-3的分泌。IL-17A的作用比IL-17F诱导的作用相对更强。与IL-17A和IL-17F诱导的作用相比，IL-17B、IL-17C、IL-17D和IL-17E的作用较弱。IL-17A和IL-17F均增强了IL-1β诱导的IL-6、IL-8、LIF、MMP-1和MMP-3的分泌。在肿瘤坏死因子（TNF）-α诱导的细胞因子和MMP分泌中也观察到了类似的增强作用。IL-17A和IL-17F早在刺激后15分钟就迅速诱导细胞外信号调节激酶（ERK）1/2、p38 MAPK和c-Jun氨基末端激酶（JNK）的磷酸化。ERK（PD98059和U0216）和p38 MAPK（SB203580）的抑制剂显著降低了IL-17F诱导的IL-6、IL-8、LIF、MMP-1和MMP-3的分泌。
结论
在IL-17家族成员中，IL-17A和IL-17F强烈刺激人结肠SEMFs，诱导炎症反应。
Zotero 插件