Inhibitory effect of carnosine on interleukin-8 production in intestinal epithelial cells through translational regulation

ABSTRACT The ability of some typical enteropathogenic Escherichia coli (EPEC) strains to adhere to, invade, and increase interleukin-8 (IL-8) production in intestinal epithelial cells in vitro has been demonstrated. However, few studies regarding these aspects have been performed with atypical EPEC (aEPEC) strains, which are emerging enteropathogens in Brazil. In this study, we evaluated a selected aEPEC strain (1711-4) of serotype O51:H40, the most prevalent aEPEC serotype in Brazil, in regard to its ability to adhere to and invade Caco-2 and T84 cells and to elicit IL-8 production in Caco-2 cells. The role of flagella in aEPEC 1711-4 adhesion, invasion, and IL-8 production was investigated by performing the same experiments with an isogenic aEPEC mutant unable to produce flagellin (FliC), the flagellum protein subunit. We demonstrated that this mutant (fliC mutant) had a marked decrease in the ability to adhere to T84 cells and invade both T84 and Caco-2 cells in gentamicin protection assays and by transmission electron microscopy. In addition, the aEPEC 1711-4 fliC mutant had a reduced ability to stimulate IL-8 production by Caco-2 cells in early (3-h) but not in late (24-h) infections. Our findings demonstrate that flagella of aEPEC 1711-4 are required for efficient adhesion, invasion, and early but not late IL-8 production in intestinal epithelial cells in vitro.

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Intestinal epithelial cells express functional interleukin-8-receptors

Gastroenterology ◽

10.1016/s0016-5085(03)82401-0 ◽

2003 ◽

Vol 124 (4) ◽

pp. A475

Author(s):

Andreas Sturn ◽

Johanna Harder-D'heureuse ◽

Brtram Wiedenmann ◽

Axel U. Dignass

Keyword(s):

Epithelial Cells ◽

Intestinal Epithelial Cells ◽

Interleukin 8 ◽

Intestinal Epithelial

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JunD enhances miR-29b levels transcriptionally and posttranscriptionally to inhibit proliferation of intestinal epithelial cells

AJP Cell Physiology ◽

10.1152/ajpcell.00027.2015 ◽

2015 ◽

Vol 308 (10) ◽

pp. C813-C824 ◽

Cited By ~ 11

Author(s):

Tongtong Zou ◽

Jaladanki N. Rao ◽

Lan Liu ◽

Lan Xiao ◽

Hee Kyoung Chung ◽

...

Keyword(s):

Cell Proliferation ◽

Transcription Factor ◽

Epithelial Cells ◽

Transcriptional Activation ◽

Binding Sites ◽

Intestinal Epithelial Cells ◽

Inhibitory Effect ◽

Microrna Expression ◽

Intestinal Epithelial ◽

Gut Epithelium

Through its actions as component of the activating protein-1 (AP-1) transcription factor, JunD potently represses cell proliferation. Here we report a novel function of JunD in the regulation of microRNA expression in intestinal epithelial cells (IECs). Ectopically expressed JunD specifically increased the expression of primary and mature forms of miR-29b, whereas JunD silencing inhibited miR-29b expression. JunD directly interacted with the miR-29b1 promoter via AP-1-binding sites, whereas mutation of AP-1 sites from the miR-29b1 promoter prevented JunD-mediated transcriptional activation of the miR-29b1 gene. JunD also enhanced formation of the Drosha microprocessor complex, thus further promoting miR-29b biogenesis. Cellular polyamines were found to regulate miR-29b expression by altering JunD abundance, since the increase in miR-29b expression levels in polyamine-deficient cells was abolished by JunD silencing. In addition, miR-29b silencing prevented JunD-induced repression of IEC proliferation. Our findings indicate that JunD activates miR-29b by enhancing its transcription and processing, which contribute to the inhibitory effect of JunD on IEC growth and maintenance of gut epithelium homeostasis.

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