Expression of human beta-defensins 1 and 2 in kidneys with chronic bacterial infection.
BACKGROUND
Constitutive expression and localization of antimicrobial human beta-defensin-1 (HBD-1) in human kidneys as a potential mechanism of antimicrobial defense has been previously reported. Inducible expression of human beta-defensin-2 (HBD-2) has been described in various epithelial organs but not for the urogenital tract.


METHODS
We investigated the gene- and protein expression of HBD-1 and HBD-2 by reverse transcriptase-polymerase chain reaction, and immunohistochemistry in 15 normal human kidney samples and 15 renal tissues with chronic bacterial infection. Additionally, cell culture experiments were performed to study HBD gene expression by real-time RT-PCR in response to inflammatory cytokines TNFalpha and IL-1beta as well as lipopolysaccharide from Gram-negative bacteria.


RESULTS
Constitutive HBD-1 gene- and protein expression was detected in normal renal tissue and kidneys with chronic infection. As a novel finding, inducible HBD-2 gene- and protein expression was demonstrated in tubulus epithelia with chronic infection but not in normal renal tissue. In pyelonephritic kidneys HBD-1 and HBD-2 expression showed a similar pattern of localization in distal tubules, loops of Henle and in collecting ducts of the kidney. Furthermore, real-time RT-PCR of kidney derived cell lines stimulated with inflammatory agents TNF-alpha, IL-1beta and LPS revealed a strong increase in relative HBD-2 transcription level and also a slight increase in relative HBD-1 transcription level.


CONCLUSIONS
Upregulated HBD-2 expression in renal tubulus epithelium indicates a role of a wider range of human defensins for antimicrobial host defense in the urogenital tract than previously recognized.
Lehmann
Jan
J
Department of Urology and Pediatric Urology, Saarland University 66421 Homburg/Saar, Germany. jan.lehmann@uniklinik-saarland.de
Retz
Margitta
M
Harder
Jürgen
J
Krams
Matthias
M
Kellner
Udo
U
Hartmann
Julia
J
Hohgräwe
Kerstin
K
Raffenberg
Uta
U
Gerber
Martin
M
Loch
Tillmann
T
Weichert-Jacobsen
Klaus
K
Stöckle
Michael
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D001424:Bacterial Infections / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007668:Kidney / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D014407:Tumor Cells, Cultured; D023083:beta-Defensins / Q000096:biosynthesis*
C406407:DEFB1 protein, human; C106641:DEFB4A protein, human; D023083:beta-Defensins