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From the Departments of Pathology,
Urology,*
and Obstetrics and
Gynecology,
University of Innsbruck,
Innsbruck, Austria
Peritoneal mesothelial cells are uniquely located to regulate
cellular events in the peritoneal cavity and are an important source
for various cytokines and growth factors. This study was conducted to
analyze the capacity of human peritoneal mesothelial cells (HPMCs) to
synthesize and release basic fibroblast growth factor (bFGF) and to
characterize its regulation by inflammatory cytokines. HPMCs
constitutively synthesized and released considerable amounts of bFGF as
detected by a specific immunoassay. Almost 80% of bFGF (1547 ±
173 pg/105 cells) was localized intracellularly.
Approximately 20% of the bFGF (357 ± 27 pg/105
cells) was associated with extracellular matrix components on the HPMC
surface. Small amounts of bFGF (<1%) were detectable in tissue
culture supernatants (8.4 ± 1.4 pg/105 cells).
Treatment of HPMCs with interleukin-1ß (IL-1ß; 1 ng/ml) resulted in
a significant increase in bFGF production. The intracellular bFGF
content showed a rapid but only transient increase, which was
significant above background levels after 24 hours (41% increase;
P < 0.05). This increase in intracellular bFGF
concentration was associated with an induction of the release of bFGF.
Within 96 hours, the release of bFGF to the cell surface and
into the supernatant increased by 58% (564 ± 52.4
pg/105 cells; P < 0.01) and by 214%
(26.4 ± 3.2 pg/105 cells; P <
0.001), respectively. Neither tumor necrosis factor-
nor
interferon-
affected bFGF synthesis by HPMCs. Stimulation of HPMCs
with IL-1ß increased steady-state levels of bFGF-specific mRNA.
Immunohistochemical analyses of peritoneal tissue revealed constitutive
expression of bFGF by HPMCs. This in situ expression
proved to be most pronounced in areas of serosal inflammation in
activated HPMCs. Our study demonstrates that HPMCs synthesize and
release significant amounts of bFGF and that the expression of this
growth factor is significantly up-regulated by the proinflammatory
cytokine IL-1ß. The data support the view that HPMCs are key
regulators of abdominal disease processes such as peritonitis,
peritoneal fibrosis, or peritoneal tumor
metastasis.
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