RENAL TUBULAR EPITHELIAL-CELL ESCHERICHIA-COLI INTERACTION PRODUCTS STIMULATE NITRIC-OXIDE PRODUCTION IN CULTURED RAT RENAL MEDULLARY INTERSTITIAL AND MESANGIAL CELLS

Tubulointerstitial and periglomerular inflammation and fibrosis are im portant consequences of pyelonephritis. The pathogenesis of these abno rmalities is not fully understood. Renal tubular epithelial cells (RTE C) elaborate biologically active materials following incubation with b acteria. Nitric oxide (NO) is an inflammatory mediator and it modulate s the accumulation of extracellular matrix proteins. Therefore, we stu died whether RTEC-E. coli interaction products regulate NO production by cultured rat renal medullary interstitial cells (RMIC) and mesangia l cells (MC). RMIC and MC were maintained in media containing IFN-gamm a and LPS for 24-72 h. Test media contained either no further additive s or 20% supernatants from RTEC incubated with E. coli or bacterial ce ll products. RTEC-E. coil interaction products significantly increased NO production in RMIC and MC. This stimulation in NO production was n ot associated with changes in inducible nitric oxide synthase (iNOS) g ene or protein expression. These findings indicate that RTEC-E, coil i nteraction products increase NO production in RMIC and MC by directly stimulating iNOS enzymatic activity. Altered NO production by renal ce lls may contribute to tubulointerstitial inflammation in acute and chr onic pyelonephritis.