IFN-纬 renders human intestinal epithelial cells responsive to lipopolysaccharide of Vibrio cholerae by down-regulation of DMBT1

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• 作者：Seok-Seong Kang^a ; ^b ; Jun Ho Jeon^c ; Sun-Je Woo^a ; ^b ; Jae Seung Yang^b ; Kyoung Whun Kim^c ; Cheol-Heui Yun^c ; Seung Hyun Han^a ; ^b ; ^{shhan-mi@snu.ac.kr}
• 关键词：Deleted in malignant brain tumor 1 ; Interferon-纬 ; Interleukin-8 ; Intestinal epithelial cells ; Lipopolysaccharide ; Vibrio cholerae
• 刊名：Comparative Immunology ; Microbiology and Infectious Diseases
• 出版年：2012
• 期刊代码：52_01479571
• 类别：bio
• 出版时间：July, 2012
• 卷：35
• 期：4
• 页码：345-354
• 文件大小：808 K

摘要

Although intestinal epithelial cells (IECs) are continuously exposed to high densities of enteric bacteria, they are not highly responsive to microbe-associated molecular patterns (MAMPs). However, inflammatory cytokines such as interferon-纬 (IFN-纬) are potentially capable of priming IECs to enhance responsiveness to MAMPs. In this study, we observed that heat-killed Vibrio cholerae (HKVC) and its lipopolysaccharide (LPS) poorly induced IL-8 production in a human IEC line, HT-29. However, both HKVC and the LPS showed a substantial induction of IL-8 production in IFN-纬-primed HT-29 cells. LPS-induced IL-8 production was proportional to the IFN-纬-priming period and LPS could not induce IL-8 production in the presence of polymyxin B. Moreover, LPS-induced IL-8 production in the IFN-纬-primed HT-29 cells was mediated through signaling pathways requiring p38 kinase and ERK, but not the JNK/SAPK pathway. Since deleted in malignant brain tumor 1 (DMBT1) is known to interact with and antagonize the action of LPS, we hypothesized that IFN-纬 enhanced the responsiveness to LPS in HT-29 through down-regulation of DMBT1. We found that IFN-纬 indeed attenuated DMBT1 expression at both the mRNA and protein levels in HT-29 cells. Conversely, when the cells were transfected with small interfering RNA to specifically silence DMBT1, IL-8 expression was augmented even in the absence of IFN-纬 and the augmentation was further enhanced by treatment with V. cholerae LPS. Since IFN-纬 is known to increase IFN-尾 expression in the IECs, we examined if IFN-尾 functioned similar to IFN-纬. Although IFN-尾 alone was able to induce IL-8 expression, it failed to render HT-29 cells responsive to V. cholerae LPS. In conclusion, our study suggests that IFN-纬 primes IECs to become responsive to V. cholerae and its LPS by suppressing the expression of DMBT1.