Escherichia coli porin induces proinflammatory alterations in renal tubular cells

Background/Aims: Several bacterial components may contribute to the development of renal injury during Gram-negative sepsis. In the present study, we evaluated the proinflammatory effect on cultured human proximal tubular epithelial cells (PTEC) of a 36-kD porin purified from Escherichia coli Methods: PTEC were stimulated with E. coli porin to evaluate ⁴⁵Ca²⁺ influx, cytoskeleton changes, generation of reactive oxygen species (ROS) as detected by chemiluminescence and cytochrome c reduction. Production of TNF- α, IL-6 and IL-8 was evaluated at the mRNA and protein levels. Results: Stimulation of PTEC with porin was followed by a rapid and sustained ⁴⁵Ca²⁺ influx and by an altered distribution of actin fibers and of vinculin streaks. Porin was able to induce generation of ROS and production of proinflammatory cytokines from PTEC. TNF-α production peaked at 6 h after exposure to porin and preceded that of IL-6 and IL-8. Conclusion: E. coli porin - at doses attainable in vivo - appears to stimulate PTEC to produce ROS and cytokines. Porin-induced PTEC activation may contribute to renal injury in the course of Gram-negative infection.