Project 1
Prevention of sepsis-induced renal proximal
tubular cell injury: prostaglandin uptake transporter PGT as a
therapeutic target
The increase during sepsis in the plasma levels of inflammatory cytokines may result in renal proximal
tubular cell (PTC) injury, thereby contributing to acute renal injury and mortality. Our preliminary results
suggest that an increase in intracellular prostaglandin E2, triggered by cytokines such as TNF-α, IFN-γ,
IL-2 e IL-1β (which are frequently increased in plasmas from septic patients) plays a relevant role in
cytokine-induced PTC injury. Therefore, inhibitors of prostaglandin reuptake transporter PGT such as
bromosulfophthalein would protect PTC against the noxious effects of inflammatory cytokines during sepsis.
The present project is aimed to confirm that i) plasmas from septic patients induce PTC injury and that both
inflammatory cytokines and intracellular prostaglandin E2 play a relevant role in PTC injury and ii) that
bromosulfophthalein prevents PTC injury sepsis-induced PTC injury in vivo (bacterial lipopolysaccharide
murine model of sepsis) as well as in vitro (PTC injury by inflammatory cytokynes).
The expected results will help to understand how are directly injured PTC by inflammatory cytokines during
sepsis, to assess the efficacy of bromosulfophthalein in the prevention of inflammatory cytokine-induced PTC
injury and to stablish the scientific basis of and the therapeutic utility of the pharmacological inhibition
of the PGT transporter.
