Basic fibroblast growth factor synthesis by human peritoneal mesothelial cells - Induction by interleukin-1

Peritoneal mesothelial cells are uniquely located to regulate cellular even ts in the peritoneal cavity and are an important source for various cytokin es 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 infla mmatory cytokines. HPMCs constitutively synthesized and released considerab le amounts of bFGF as detected by a specific immunoassay. Almost 80% of bFG F (1547 +/- 173 pg/10(5) cells) was localized intracellularly, Approximatel y 20% of the bFGF (357 +/- 27 pg/10(5) cells) was associated with extracell ular matrix components on the HPMC surface. Small amounts of bFGF (<1%) wer e detectable in tissue culture supernatants (8.4 +/- 1.4 pg/10(5) cells). T reatment of HPMCs with interleukin-1 beta (IL-1 beta; 1 ng/ml) resulted in a significant increase in bFGF production. The intracellular bFGF content s howed a rapid but only transient increase, which was significant above back ground levels after 24 hours (41% increase; P < 0.05). This increase in int racellular bFGF concentration was associated with an induction of the relea se of bFGF, Within 96 hours, the release of bFGF to the cell surface and in to the supernatant increased by 58% (564 +/- 52.4 pg/10(5) cells; P < 0.01) and by 214% (26.4 +/- 3.2 pg/10(5) cells; P < 0.001), respectively. Neithe r tumor necrosis factor-alpha nor interferon-gamma affected bFGF synthesis by HPMCs. Stimulation of HPMCs with IL-1 beta increased steady-state levels of bFGF-specific mRNA, Immunohistochemical analyses of peritoneal tissue r evealed constitutive expression of bFGF by HPMCs. This in situ expression p roved to be most pronounced in areas of serosal inflammation in activated H PMCs. Our study demonstrates that HPMCs synthesize and release significant amounts of bFGF and that the expression of this growth factor is significan tly up-regulated by the proinflammatory cytokine IL-1 beta. The data suppor t the view that HPMCs are key regulators of abdominal disease processes suc h as peritonitis, peritoneal fibrosis, or peritoneal tumor metastasis.