Renal tubular epithelial cell-E. coli interaction products stimulate nitric oxide production in cultured rat renal medullary interstitial and mesangial cells.
Tubulointerstitial and periglomerular inflammation and fibrosis are important consequences of pyelonephritis. The pathogenesis of these abnormalities is not fully understood. Renal tubular epithelial cells (RTEC) elaborate biologically active materials following incubation with bacteria. Nitric oxide (NO) is an inflammatory mediator and it modulates the accumulation of extracellular matrix proteins. Therefore, we studied whether RTEC-E. coli interaction products regulate NO production by cultured rat renal medullary interstitial cells (RMIC) and mesangial cells (MC). RMIC and MC were maintained in media containing IFN-gamma and LPS for 24-72 h. Test media contained either no further additives or 20% supernatants from RTEC incubated with E. coli or bacterial cell products. RTEC-E. coli interaction products significantly increased NO production in RMIC and MC. This stimulation in NO production was not associated with changes in inducible nitric oxide synthase (iNOS) gene or protein expression. These findings indicate that RTEC-E. coli interaction products increase NO production in RMIC and MC by directly stimulating iNOS enzymatic activity. Altered NO production by renal cells may contribute to tubulointerstitial inflammation in acute and chronic pyelonephritis.
Trachtman
H
H
Department of Pediatrics, Schneider Children's Hospital, New Hyde Park, NY 11040-1432, USA. trachtma@lij.edu
Futterweit
S
S
Singhal
P C
PC
Sankaran
R
R
Franki
N
N
D000818:Animals; D002450:Cell Communication / Q000502:physiology*; D003470:Culture Media; D004848:Epithelium / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism*; D005920:Glomerular Mesangium / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology; D007679:Kidney Medulla / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D051381:Rats
D003470:Culture Media; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D007371:Interferon-gamma