title: Cooperation of interleukin-17 and interferon-gamma on chemokine secretion in human fetal intestinal epithelial cells.
abstract: Interleukin (IL)-17 is a newly identified T cell-derived cytokine that can regulate the functions of a variety of cell types. In this study, we investigated the effects of IL-17 and interferon (IFN)-gamma on chemokine secretion in human fetal intestinal epithelial cells. IL-8 and monocyte chemoattractant protein (MCP)-1 secretion by the human fetal intestinal epithelial cell line, intestine-407, was evaluated by ELISA and Northern blot. The expression of IL-17 receptor (R) was analysed by a binding assay using [(125)I]-labelled IL-17. The activation of nuclear factor-kappa B (NF-kappa B), NF-IL6 and AP-1 was assessed by an electrophoretic gel mobility shift assay (EMSA). IL-17 induced a dose-dependent increase in IL-8 and MCP-1 secretion. The inducing effects of IL-17 on IL-8 and MCP-1 mRNA abundance reached a maximum as early as 3 h, and then gradually decreased. IL-17 and IFN-gamma synergistically increased IL-8 and MCP-1 secretion and mRNA abundance. IFN-gamma induced a weak increase in IL-17 R mRNA abundance, and incubation with IFN-gamma for 24 h enhanced [(125)I]-labelled IL-17-binding by 2.4-fold. IL-17 rapidly induced the phosphorylation and degradation of I kappa B alpha molecules, and the combination of IL-17 and IFN-gamma induced a marked increase in NF-kappa B DNA-binding activity as early as 1.5 h after the stimulation. Furthermore, this combination induced an increase in NF-IL-6 and AP-1 DNA-binding activity. In conclusion, it becomes clear that IL-17 is an inducer of IL-8 and MCP-1 secretion by human fetal intestinal epithelial cells. The combination of IL-17 with IFN-gamma synergistically enhanced chemokine secretion. These effects of IL-17 and IFN-gamma might play an important role in the inflammatory responses in the intestinal mucosa.
authors.affiliation: Department of Internal Medicine, Shiga University of Medical Science, Seta-Tukinowa, Japan. andoh@belle.shiga-med.ac.jp
authors.forename: A
authors.initials: A
authors.lastname: Andoh
authors.forename: H
authors.initials: H
authors.lastname: Takaya
authors.forename: J
authors.initials: J
authors.lastname: Makino
authors.forename: H
authors.initials: H
authors.lastname: Sato
authors.forename: S
authors.initials: S
authors.lastname: Bamba
authors.forename: Y
authors.initials: Y
authors.lastname: Araki
authors.forename: K
authors.initials: K
authors.lastname: Hata
authors.forename: M
authors.initials: M
authors.lastname: Shimada
authors.forename: T
authors.initials: T
authors.lastname: Okuno
authors.forename: Y
authors.initials: Y
authors.lastname: Fujiyama
authors.forename: T
authors.initials: T
authors.lastname: Bamba
mesh_terms: D002460:Cell Line; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D015870:Gene Expression; D006801:Humans; D020672:I-kappa B Proteins; D007371:Interferon-gamma / Q000276:immunology* / Q000494:pharmacology; D020381:Interleukin-17 / Q000276:immunology* / Q000494:pharmacology; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D007413:Intestinal Mucosa / Q000166:cytology / Q000196:embryology / Q000276:immunology*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D018123:Receptors, Interleukin / Q000235:genetics; D053722:Receptors, Interleukin-17; D011994:Recombinant Proteins / Q000235:genetics; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D018932:Chemokine CCL2; D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; C109985:IL17RA protein, human; D020381:Interleukin-17; D016209:Interleukin-8; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D018123:Receptors, Interleukin; D053722:Receptors, Interleukin-17; D011994:Recombinant Proteins; D018808:Transcription Factor AP-1; D000072000:NF-KappaB Inhibitor alpha; D007371:Interferon-gamma