Differential expression of interleukin-15, a pro-inflammatory cytokine and T-cell growth factor, and its receptor in human prostate.
BACKGROUND
Pro-inflammatory interleukin (IL)-15 plays a major role in host defense and chronic inflammation by stimulating T-lymphocyte recruitment and growth. Expression of IL-15 and IL-15 receptor (IL-15R) in human prostate was examined.


METHODS
Normal and benign hyperplastic (BPH) prostate specimens (n = 23) were analyzed for IL-15 and IL-15Ralpha-chain expression by immunohistochemistry and Real-Time-PCR/RT-PCR. Regulation of prostatic stromal cell (PSC) IL-15 mRNA and effect of IL-15 on prostatic cell growth were analysed in vitro.


RESULTS
In normal prostate, anti-IL-15 and anti-IL-15Ralpha-chain reactivity were restricted to smooth muscle and stromal cells. However, in BPH, in addition epithelial cells frequently exhibited discrete anti-IL-15R and often intense, membranous anti-IL-15 reactivity. IL-15/IL-15R mRNA were detected in all prostatic cells types. In BPH tissues, IL-15 mRNA content was variable (15-fold). IL-15 mRNA synthesis of PSC was significantly up-regulated by IFN-gamma. Furthermore IL-15 strongly stimulated the growth of BPH-T-lymphocytes and weakly that of carcinoma cell lines, but not of stromal cells.


CONCLUSIONS
Overexpression of IL-15 and IL-15Ralpha-chain in BPH and massive proliferation of BPH-T-lymphocytes induced by IL-15 suggest a role for IL-15 in prostatic inflammation. Since IFN-gamma, a T-lymphocyte product, stimulates prostatic IL-15 production; chronic inflammation might be triggered by this paracrine loop.
Handisurya
A
A
Department of Urology, University of Vienna, Vienna, Austria.
Steiner
G E
GE
Stix
U
U
Ecker
R C
RC
Pfaffeneder-Mantai
S
S
Langer
D
D
Kramer
G
G
Memaran-Dadgar
N
N
Marberger
M
M
D000293:Adolescent; D000328:Adult; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D018076:DNA, Complementary / Q000737:chemistry; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D019409:Interleukin-15 / Q000032:analysis / Q000096:biosynthesis*; D053613:Janus Kinase 1; D008297:Male; D011467:Prostate / Q000378:metabolism* / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000032:analysis / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; C508024:IL15RA protein, human; D019409:Interleukin-15; D012333:RNA, Messenger; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; D053613:Janus Kinase 1