Warhurst A C, Hopkins S J, Warhurst G
Department of Surgery, Hope Hospital, Salford, UK.
Gut. 1998 Feb;42(2):208-13. doi: 10.1136/gut.42.2.208.
Production of chemoattractant factors by the intestinal epithelium may contribute to mucosal infiltration by inflammatory cells in inflammatory bowel disease. Secretion of the alpha chemokine interleukin 8 (IL-8), a neutrophil chemoattractant, has been widely studied, but little is known about epithelial secretion of beta chemokines, which are preferentially involved in recruiting monocytes.
To investigate the profiles of alpha and beta chemokine secretion in colonic cell lines and their differential modulation by interferon gamma (IFN-gamma), a product of activated T lymphocytes and natural killer cells.
HT29-19A, a model of the CT secretory crypt cell, exhibited a parallel secretion of the alpha chemokines IL-8 and GRO alpha, which could be markedly upregulated by tumour necrosis factor alpha (TNF-alpha) and IL-1 beta. These cells showed no significant expression of the beta chemokines RANTES (regulated upon activation T cell expressed and secreted), MIP-1 alpha (macrophage inflammatory protein 1 alpha), and MCP-1 (monocyte chemotactic protein 1) under these conditions, but IFN-gamma in combination with TNF-alpha caused a dose dependent induction of RANTES and MCP-1 secretion. This was accompanied by a marked increase of RANTES mRNA. In contrast, IFN-gamma had no significant effect on TNF-alpha stimulated IL-8 secretion. Caco-2 cells, with features more typical of villus absorptive cells, were relatively poor secretors of alpha chemokines but secreted high levels of MCP-1 in response to IL-1 beta. IFN-gamma did not influence alpha or beta chemokine secretion in these cells.
These studies suggest that intestinal epithelial cells may produce chemokines capable of attracting both neutrophils and monocytes. The ability of IFN-gamma to activate the expression of beta chemokines preferentially could facilitate the development of chronic inflammatory infiltrates.
肠道上皮细胞产生的趋化因子可能在炎症性肠病中促使炎症细胞浸润黏膜。α趋化因子白细胞介素8（IL - 8）作为一种中性粒细胞趋化剂，其分泌已得到广泛研究，但对于优先参与募集单核细胞的β趋化因子的上皮分泌情况却知之甚少。
研究结肠细胞系中α和β趋化因子的分泌谱及其受活化T淋巴细胞和自然杀伤细胞产物γ干扰素（IFN - γ）的差异调节情况。
HT29 - 19A作为CT分泌性隐窝细胞模型，呈现出α趋化因子IL - 8和GROα的平行分泌，肿瘤坏死因子α（TNF - α）和白细胞介素1β（IL - 1β）可使其显著上调。在这些条件下，这些细胞未显示出β趋化因子调节激活正常T细胞表达和分泌的趋化因子（RANTES）、巨噬细胞炎性蛋白1α（MIP - 1α）和单核细胞趋化蛋白1（MCP - 1）的显著表达，但IFN - γ与TNF - α联合可导致RANTES和MCP - 1分泌呈剂量依赖性诱导。这伴随着RANTES mRNA的显著增加。相比之下，IFN - γ对TNF - α刺激的IL - 8分泌无显著影响。具有更典型绒毛吸收细胞特征的Caco - 2细胞是α趋化因子的相对较弱分泌者，但对IL - 1β反应时分泌高水平的MCP - 1。IFN - γ不影响这些细胞中α或β趋化因子的分泌。
这些研究表明肠道上皮细胞可能产生能够吸引中性粒细胞和单核细胞的趋化因子。IFN - γ优先激活β趋化因子表达的能力可能促进慢性炎症浸润的发展。
