International Immunology, Vol. 13, No. 10, 1255-1263,
October 2001
© 2001 Japanese Society for Immunology
Proinflammatory cytokines induce liver and activation-regulated chemokine/macrophage inflammatory protein-3
/CCL20 in mucosal epithelial cells through NF-
B
1 Departments of Surgery II and
2 Microbiology, Kinki University School of Medicine, Osaka-Sayama, Osaka 589-8511, Japan
Correspondence to: Correspondence to: K. Hieshima
Liver and activation-regulated chemokine (LARC)/CCL20 is expressed by surface-lining epithelial and epidermal cells, and is likely to link innate and acquired immunity by attracting immature dendritic cells, effector memory T cells and B cells via CCR6. Here we examined the mechanism of LARC expression in epithelial-type cells. Either IL-1ß or tumor necrosis factor (TNF)-
strongly induced LARC mRNA in intestinal cell lines Caco-2 and T84, while both were effective on HEK 293T cells. Induction of LARC was also demonstrated in the intestinal epithelium of BALB/c mice upon treatment with IL-1 or TNF-. Transient transfection assays using murine LARC promoter–reporter constructs identified a region essential for IL-1ß- or TNF--induced promoter activation in Caco-2 and 293T cells. Using site-directed mutagenesis, we demonstrated that an NF-
B site located between –96 and –87 bp upstream from the transcriptional start site was both necessary and sufficient for IL-1ß- or TNF--induced promoter activation in Caco-2 and 293T cells. Electrophoretic mobility shift assays demonstrated that p50/p65 heterodimer and p65 homodimer of NF-B bound to this site in 293T cells upon treatment with IL-1ß and TNF-, and p50/p65 heterodimer bound to this site in Caco-2 cells upon treatment with IL-1ß. Co-expression of constitutively active p65 strongly activated the promoter construct carrying the intact NF-B site in 293T and Caco-2 cells. Collectively, LARC expression in intestinal epithelial-type cells is induced by proinflammatory cytokines such as IL-1 and TNF- primarily through activation of NF-B.
Keywords: chemokine, epithelial cell, IL-1, NF-B, tumor necrosis factor, small intestine
Transmitting editor: K. Sugamura
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