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Título:

Crosstalk between Human Microvascular Endothelial Cells and Tubular Epithelial Cells Modulates Pro-Inflammatory Responses Induced by Shiga Toxin Type 2 and Subtilase Cytotoxin

Autor/es:

ALVAREZ ROMINA; JANCIC CAROLINA; GARIMANO NICOLAS; SACERDOTI FLAVIA; PATON ADRIENNE; PATON JAMES; CRISTINA IBARRA; AMARAL MARÍA MARTA

Revista:

Toxins (Basel)

Editorial:

MDPI

Referencias:

Año: 2019

ISSN:

2072-6651

Resumen:

Hemolytic uremic syndrome is aconsequence of Shiga toxin (Stx)-producing Escherichia coli (STEC) infectionand is the most frequent cause of acute renal failure (ARF) in children.Subtilase cytotoxin (SubAB) has also been associated with Hemolytic Uremic Syndrome pathogenesis. We previously reported that Stx2 and SubAB causedifferent effects on co-cultures of human renal microvascular endothelial cells(HGEC) and human proximal tubular epithelial cells (HK-2) relative to HGEC andHK-2 monocultures. In this work we have analyzed the secretion ofpro-inflammatory cytokines by co-cultures compared to monocultures exposed ornot to Stx2, SubAB, and Stx2+SubAB. Under basal conditions, IL-6, IL-8 andTNF-α secretion was different between monocultures and co-cultures. After toxintreatments, high concentrations of Stx2 and SubAB decreased cytokine secretionby HGEC monocultures, but in contrast, low toxin concentrations increased theirrelease. Toxins did not modulate the cytokine secretion by HK-2 monocultures,but increased their release in the HK-2 co-culture compartment. In addition,HK-2 monocultures were stimulated to release IL-8 after incubation with HGECconditioned media. Finally, Stx2 and SubAB were detected in HGEC and HK-2 cellsfrom the co-cultures. This work describes, for the first time, the inflammatoryresponses induced by Stx2 and SubAB, in a crosstalk model of renal endothelialand epithelial cells.

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