Analysis of the inflammatory network in benign prostate hyperplasia and prostate cancer.
BACKGROUND
The complexity of acute and chronic inflammatory processes may either lead to benign prostate hyperplasia (BPH) and/or prostate cancer. Obviously, various tissue cells are activated by chemokines via different chemotaxin receptors which then trigger subsequent processes in angiogenesis, cellular growth, and extravasation as well as neoplasia.


METHODS
Using the surgically obtained tissue of patients (n = 36) with BPH or prostate carcinoma (PCA), we studied among others the expression of chemokines (Rantes, IL-8), chemotaxin receptors (CXCR-3 and -4, CCR-3, CCR-5), of matrixmetalloproteinases (MMP-2 and 9), of Toll-like (TL) receptors 1, 2, 3, 4, 5, 7, and 9 and of the inducible cyclooxygenase-2 (cox-2) by RT-PCR. Further support for the different properties of tissue from PCA was obtained using two different PCA cell lines (PC3 = androgen resistant cell) or LNCAP cells (androgen sensitive) with emphasis on IL-8, Il-6, and PGE(2) release. Cell lines were stimulated with either the tumor necrosis factor-alpha (TNF-alpha) and lipopolysacharide (LPS) over time. In addition to cytokine release, the quantification of mRNA by lightcycler for cox-2, IL-6, and IL-8 was performed on these cell lines.


RESULTS
Remarkable differences in expression were obtained by RT-PCR when BPH tissue versus PCA was analyzed. Expression of CXCR-1 after incubation with LPS and TNF-alpha showed time-dependent differences for androgen-sensitive LNCAP as compared to androgen-resistant PC-3 cells. TNF-alpha incubation leads to a time-dependent induction of cox-2 expression unlike to activation with LPS. Differences with regard to cox-2, IL-6, and IL-8 expression were seen by quantitative lightcycler analysis. Significant differences were also observed when TL receptors 4, 5, 7, and 9 were analyzed which were significantly expressed in BPH- as compared to PCA-tissue.


CONCLUSIONS
Our data clearly demonstrate that various inflammatory and cell biological cascades are involved which either lead to BPH or can be linked to the development of PCA. The exact cell biological mechanisms may provide novel therapeutic options in the treatment of both diseases.
König
Jens Ekkehard
JE
Department of Urology, Ruhr-Universität Bochum, Marienhospital Herne, Herne, Germany. Jens.e.koenig@ruhr-uni-bochum.de
Senge
Theodor
T
Allhoff
Ernst Peter
EP
König
Wolfgang
W
D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D002471:Cell Transformation, Neoplastic; D002630:Chemotactic Factors / Q000276:immunology; D002908:Chronic Disease; D051546:Cyclooxygenase 2; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007249:Inflammation; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D016209:Interleukin-8 / Q000096:biosynthesis / Q000276:immunology; D007527:Isoenzymes / Q000096:biosynthesis / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000276:immunology; D011470:Prostatic Hyperplasia / Q000276:immunology*; D011471:Prostatic Neoplasms / Q000276:immunology*; D023062:Receptors, Interleukin-8A / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D002630:Chemotactic Factors; D016207:Cytokines; D015850:Interleukin-6; D016209:Interleukin-8; D007527:Isoenzymes; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D023062:Receptors, Interleukin-8A; D014409:Tumor Necrosis Factor-alpha; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases