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.

The superior prognostic value of humoral factors compared with molecular proliferation markers in renal cell carcinoma.

BACKGROUND: The American Joint Committee on Cancer and the Union Internationale Contre le Cancer have acknowledged routine laboratory parameters, such as serum calcium, alkaline phosphatase, hemoglobin, and the erythrocyte sedimentation rate (ESR), as predictors of survival in patients with renal cell carcinoma. The predictive value of these parameters compared with proliferation markers, such as Ki-67, proliferating cell nuclear antigen (PCNA), topoisomerase II-alpha, and p100, has not been determined. METHODS: Forty-eight consecutive patients who underwent nephrectomy for nonmetastatic renal cell carcinoma between 1990 and 1994 were observed up to 120 months postoperatively. Ten of 48 patients developed tumor progression 6-69 months after surgery. Routine preoperative laboratory parameters as well as tumor-specific data were assessed. Findings were compared with tumor proliferation indices, which were obtained by immunohistochemical staining for nuclear antigens Ki-67, PCNA, topoisomerase II-alpha, and p100 in paraffin embedded tumor tissue. RESULTS: Univariate and multivariate statistical analyses demonstrated superiority of routine laboratory values compared with tumor proliferation indices in predicting progression-free survival and disease-specific death. The best predictor after tumor size and symptomatic presentation was ESR (P < 0.0001), with ESR values > 70 mm at 2 hours indicating a significantly poorer prognosis. Only the proliferation marker Ki-67 reached univariate significance at a threshold of 7%. CONCLUSIONS: Routine laboratory parameters, such as alkaline phosphatase, lactate dehydrogenase, thrombocyte count, and especially ESR, provided superior long-term prognostic information for patients with nonmetastatic renal cell carcinoma compared with the molecular tumor proliferation markers Ki-67, PCNA, topoisomerase II-alpha, and p100.