title: Escherichia coli-induced expression of IL-1 alpha, IL-1 beta, IL-6 and IL-8 in normal human renal tubular epithelial cells.
abstract: The aim of the present study was to investigate whether the IL-1 family cytokines, in addition to IL-6 and IL-8, could be induced in normal human cortical epithelial cells in response to bacterial stimuli. Human renal tissue was obtained from 9 patients undergoing elective tumour nephrectomy. Renal cortical epithelial cells of tubular origin were prepared from the unaffected tissue. The proximal tubular cells were stimulated for 2, 6 and 24 h with a heat-inactivated pyelonephritogenic Escherichia coli strain DS-17. Cultured unstimulated tubular cells served as controls. IL-1 alpha, IL-1 beta, IL-1 receptor antagonist, IL-6, IL-8, IL-10, TNF-alpha, G-CSF and GM-CSF were analysed using immunohistochemistry at the single cell level. The nonstimulated cells were found to express low levels of IL-6 and IL-8 (mean value < 3% of total cells). In contrast, E. coli exposure resulted in significantly increased incidences of IL-6 and IL-8 expressing cells (mean values approximately 18% of total cells) peaking within two hours of stimulation (P < 0.008 and P < 0.02 versus non-stimulated cells, respectively). A gradual decrease was thereafter observed at 6 and 24 h, respectively, although persistently higher compared to controls. A different kinetic response was found for IL-1 alpha, IL-1 beta and IL-1 receptor antagonist-expressing cells, which peaked 24 h after E. coli stimulation (mean values 3--10%) (P < 0.008, P < 0.02, P < 0.02 versus non-stimulated cells, respectively). Low levels of TNF-alpha and GM-CSF were found in 3 of the 9 donated epithelial cells, peaking at 2 h, and IL-10 and G-CSF producing cells in 1 patient each. In conclusion we found that heat-inactivated pyelonephritic E. coli induced a proinflammatory cytokine response in the normal human proximal tubular cells including the IL-1 family, IL-6 and IL-8.
authors.affiliation: Department of Microbiology, Nephrology, Astrid Lindgren Children's Hospital, Karolinska Hospital and Karolinska Institute, Stockholm, Sweden. Annelie.Brauner@ks.se
authors.forename: A
authors.initials: A
authors.lastname: Brauner
authors.forename: M
authors.initials: M
authors.lastname: Söderhäll
authors.forename: S H
authors.initials: SH
authors.lastname: Jacobson
authors.forename: J
authors.initials: J
authors.lastname: Lundahl
authors.forename: U
authors.initials: U
authors.lastname: Andersson
authors.forename: J
authors.initials: J
authors.lastname: Andersson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis*; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D004926:Escherichia coli / Q000276:immunology*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D007680:Kidney Neoplasms / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor