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

ALVAREZ ROMINA S; JANCIC, CAROLINA; GARIMANO NICOLAS EZEQUIEL; SACERDOTI F; PATON AW; PATON JC; IBARRA C; AMARAL MM

Toxins (Basel)

Basel : MDPI

Lugar: Basel; Año: 2019

Hemolytic uremic syndrome (HUS) is a consequence of Shiga toxin (Stx)-producingEscherichiacoli (STEC) infection and is the most frequent cause of acute renal failure (ARF) in children. Subtilasecytotoxin (SubAB) has also been associated with HUS pathogenesis. We previously reported that Stx2and SubAB cause different effects on co-cultures of human renalmicrovascular endothelial cells (HGEC)and human proximal tubular epithelial cells (HK-2) relative to HGEC and HK-2 monocultures. Inthis work we have analyzed the secretion of pro-inflammatory cytokines by co-cultures compared tomonocultures exposed or not to Stx2, SubAB, and Stx2+SubAB. Under basal conditions, IL-6, IL-8 andTNF- secretion was different between monocultures and co-cultures. After toxin treatments, highconcentrations of Stx2 and SubAB decreased cytokine secretion by HGEC monocultures, but in contrast,low toxin concentrations increased their release. Toxins did not modulate the cytokine secretion byHK-2 monocultures, but increased their release in the HK-2 co-culture compartment. In addition, HK-2monocultures were stimulated to release IL-8 after incubation with HGEC conditioned media. Finally,Stx2 and SubAB were detected in HGEC and HK-2 cells from the co-cultures. This work describes,for the first time, the inflammatory responses induced by Stx2 and SubAB, in a crosstalk model of renalendothelial and epithelial cells.