Escherichia coli porin induces proinflammatory alterations in renal tubular cells.
OBJECTIVE
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-alpha, 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-alpha production peaked at 6 h after exposure to porin and preceded that of IL-6 and IL-8.


CONCLUSIONS
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.
Biancone
L
L
Department of Clinical and Biological Sciences, University of Pavia, Varese, Italy.
Conaldi
P G
PG
Toniolo
A
A
Camussi
G
G
D000199:Actins / Q000032:analysis; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D004848:Epithelium / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D004926:Escherichia coli; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008163:Luminescent Measurements; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D016133:Polymerase Chain Reaction; D018272:Porins / Q000302:isolation & purification / Q000633:toxicity*; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000199:Actins; D016207:Cytokines; D015850:Interleukin-6; D016209:Interleukin-8; D018272:Porins; D014409:Tumor Necrosis Factor-alpha