Kolios G, Wright K L, Jordan N J, Leithead J B, Robertson D A, Westwick J
Department of Pharmacology, University of Bath, GB.
Eur J Immunol. 1999 Feb;29(2):530-6. doi: 10.1002/(SICI)1521-4141(199902)29:02<530::AID-IMMU530>3.0.CO;2-Y.
Differential chemokine production by colonic epithelial cells is thought to contribute to the characteristic increased infiltration of selected population of leukocytes cells in inflammatory bowel disease. We have previously demonstrated that IL-13 enhances IL-1alpha-induced IL-8 secretion by the colonic epithelial cell line HT-29. We have now explored the C-C chemokine expression and modulation in this system. The combination of TNF-alpha and IFN-gamma was the minimal stimulation required for regulated on activation, normal T cell expressed and secreted (RANTES) and monocyte chemoattractant protein (MCP-1) mRNA expression and secretion by HT-29 cells. The same stimulation induced a stronger IL-8 mRNA expression and secretion. Pretreatment with IL-13 or IL-4, reduced significantly the RANTES, and MCP-1, but not IL-8 mRNA expression and secretion. In contrast, IL-10 had no effect on either MCP-1, or RANTES, or IL-8 generation. Pretreatment of HT-29 cells with wortmannin suggested that the IL-13-induced inhibition of C-C chemokine expression is via activation of a wortmannin-sensitive phosphatidylinositol 3-kinase. These data demonstrate that colonic epithelial cell chemokine production can be differentially regulated by T cell-derived cytokines and suggest an interplay between epithelial cells and T lymphocytes potentially important in the intestinal inflammation.
结肠上皮细胞产生不同的趋化因子被认为是导致炎症性肠病中特定白细胞群体浸润增加这一特征的原因。我们之前已经证明，白细胞介素-13（IL-13）可增强白细胞介素-1α（IL-1α）诱导的结肠上皮细胞系HT-29分泌白细胞介素-8（IL-8）。我们现在已经探究了该系统中C-C趋化因子的表达及调控情况。肿瘤坏死因子-α（TNF-α）和干扰素-γ（IFN-γ）的联合作用是HT-29细胞中调节激活正常T细胞表达和分泌因子（RANTES）以及单核细胞趋化蛋白（MCP-1）mRNA表达和分泌所需的最小刺激。相同的刺激诱导了更强的IL-8 mRNA表达和分泌。用IL-13或IL-4预处理可显著降低RANTES和MCP-1，但不影响IL-8 mRNA的表达和分泌。相比之下，IL-10对MCP-1、RANTES或IL-8的产生均无影响。用渥曼青霉素预处理HT-29细胞表明，IL-13诱导的C-C趋化因子表达抑制是通过激活对渥曼青霉素敏感的磷脂酰肌醇3-激酶实现的。这些数据表明，结肠上皮细胞趋化因子的产生可受到T细胞衍生细胞因子的差异调节，并提示上皮细胞与T淋巴细胞之间的相互作用在肠道炎症中可能具有重要意义。
