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标题：Developmentally regulated IκB expression in intestinal epithelium and susceptibility to flagellin-induced inflammation
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作者：Erika C. Claud ; Lei Lu ; Pauline M. Anton 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2004
卷号：101
期号：19
页码：7404-7408
DOI：10.1073/pnas.0401710101
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Necrotizing enterocolitis is a devastating inflammatory condition of the intestine that occurs almost exclusively in premature newborns. Although its exact pathogenesis is unclear, we have postulated that it may result from a predisposition of the immature intestine to mount an unusually robust and damaging response to microbial infection. In support of this idea, we report that the IL-8 response of an immature human enterocyte cell line to bacterial infection was significantly higher than that of a mature enterocyte cell line. The response in both cell lines was flagellin-dependent. Corresponding to the difference in IL-8 production, the immature enterocytes expressed appreciably lower levels of specific I{kappa}B genes when compared with the mature enterocytes. Similar developmentally regulated differences in cytokine response and I{kappa}B expression were also seen in primary rat enterocytes, indicating that these observations were not peculiarities of the cell lines. Furthermore, when the level of I{kappa}B{alpha} expression was increased in the immature cell line by transfection, the flagellin-dependent IL-8 response was attenuated. Thus, we have demonstrated a previously undescribed developmental regulation of I{kappa}B expression in the intestine involved in modulating the IL-8 response to bacterial infection, which may contribute to the pathogenesis of age-specific inflammatory bowel diseases such as necrotizing enterocolitis.