Decreased in vitro proliferation of bladder epithelial cells from patients with interstitial cystitis.
OBJECTIVE
To determine whether explanted bladder epithelial cells from patients with interstitial cystitis (IC) display intrinsically decreased rates of proliferation in vitro, and to compare the growth rates of untreated IC and normal bladder cells with the rates of normal cells treated with a purified antiproliferative factor (APF) at levels found in urine from patients with IC.


METHODS
Epithelial cell explants were prepared from the bladder biopsies of 4 patients with IC and 2 asymptomatic controls. Cell proliferation was determined by serial counting of trypan blue-negative cells. APF and mock APF were purified chromatographically, and activity was determined by (3)H-thymidine incorporation into primary normal bladder epithelial cells. Heparin-binding epidermal growth factor-like growth factor and epidermal growth factor were measured by enzyme-linked immunosorbent assay.


RESULTS
Bladder epithelial cells from patients with IC proliferated significantly less than did control cells by day 2 after serum starvation (P = 0.02). Similar inhibition of the proliferation rate was seen in control cells treated with APF; APF-induced changes in heparin-binding epidermal growth factor-like growth factor, but not epidermal growth factor, production by cells were associated with changes in growth rates.


CONCLUSIONS
The proliferation rate of explanted bladder epithelial cells from patients with IC in serum-free medium was significantly less than that of control cells, indicating an intrinsic abnormality in IC cell proliferation. This abnormality may be caused by APF, which induces reversible inhibition of heparin-binding epidermal growth factor-like growth factor production and normal bladder epithelial cell proliferation.
Keay
Susan
S
Division of Infectious Diseases, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Zhang
Chen-Ou
CO
Shoenfelt
Joanna L
JL
Chai
Toby C
TC
D000328:Adult; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D018856:Cystitis, Interstitial / Q000473:pathology*; D003558:Cystoscopy / Q000379:methods; D004815:Epidermal Growth Factor / Q000096:biosynthesis; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006131:Growth Inhibitors / Q000302:isolation & purification / Q000494:pharmacology / Q000652:urine; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D001743:Urinary Bladder / Q000378:metabolism / Q000473:pathology*
D006131:Growth Inhibitors; C587883:HBEGF protein, human; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D004815:Epidermal Growth Factor