Antibakterielle aktivität humaner renaler tubulusepithelzellen: Eine mögliche rolle der β-defensine

Renal tubular cells (RTC) form a barrier between the host and ascending microbes in upper urinary tract infection. Former studies have shown the ability of the kidney to produce defensins - antimicrobial peptides that play a pivotal role in unspecific host defence. To further clarify the role of renal epithelium for direct antibacterial activity we investigated the expression, regulation and production of antimicrobial peptides by cultured human renal tubular cells. Cellculture supernatants of renal tubular cells exert strong activity against Escherichia coli and Klebsiella pneumoniae, two of the most important pathogens in urinary tract infections. The antimicrobial effect depends on salt concentration, a typical feature of human defensins. RT-PCR of RNA from cultured proximal and distal RTC showed constitutive expression of human β-Defensin-1 (hbd-1) and human β-Defensin-2 (hbd-2) whereas only hbd-1 expression could be detected in RNA preparation from renal biopsy material. Hbd-2 expression of RTC was induced by inflammatory processes as shown by semiquantitative competitive RT-PCR. Coincubation of the cultured cells with IL-1α or E. coli promote the strongest hbd-2 induction whereas TNF-α and LPS lead to a weaker hbd-2 induction. This is the first evidence that human renal tubular cells are able to produce antibacterial substances in a biological relevant amount and that β-Defensins are candidate proteins responsible for this effect.