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

被引:46
作者
Cronauer, MV
Stadlmann, S
Klocker, H
Abendstein, B
Eder, IE
Rogatsch, H
Zeimet, AG
Marth, C
Offner, FA
机构
[1] Univ Innsbruck, Dept Pathol, A-6020 Innsbruck, Austria
[2] Univ Innsbruck, Dept Urol, A-6020 Innsbruck, Austria
[3] Univ Innsbruck, Dept Obstet & Gynecol, A-6020 Innsbruck, Austria
基金
奥地利科学基金会;
关键词
D O I
10.1016/S0002-9440(10)65516-2
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
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/10(5) cells) was localized intracellularly, Approximately 20% of the bFGF (357 +/- 27 pg/10(5) 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/10(5) cells). Treatment of HPMCs with interleukin-1 beta (IL-1 beta; 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/10(5) cells; P < 0.01) and by 214% (26.4 +/- 3.2 pg/10(5) cells; P < 0.001), respectively. Neither 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 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-1 beta. The data support the view that HPMCs are key regulators of abdominal disease processes such as peritonitis, peritoneal fibrosis, or peritoneal tumor metastasis.
引用
收藏
页码:1977 / 1984
页数:8
相关论文
共 51 条
[1]   Biological roles of fibroblast growth factor-2 [J].
Bikfalvi, A ;
Klein, S ;
Pintucci, G ;
Rifkin, DB .
ENDOCRINE REVIEWS, 1997, 18 (01) :26-45
[2]   DIFFERENTIAL STIMULATION OF COLLAGENASE AND CHEMOTACTIC ACTIVITY IN FIBROBLASTS DERIVED FROM RAT WOUND REPAIR TISSUE AND HUMAN-SKIN BY GROWTH-FACTORS [J].
BUCKLEYSTURROCK, A ;
WOODWARD, SC ;
SENIOR, RM ;
GRIFFIN, GL ;
KLAGSBRUN, M ;
DAVIDSON, JM .
JOURNAL OF CELLULAR PHYSIOLOGY, 1989, 138 (01) :70-78
[3]   THE HEPARIN-BINDING (FIBROBLAST) GROWTH-FACTOR FAMILY OF PROTEINS [J].
BURGESS, WH ;
MACIAG, T .
ANNUAL REVIEW OF BIOCHEMISTRY, 1989, 58 :575-606
[4]  
CARTER D, 1997, HISTOLOGY PATHOLOGIS, P2299
[5]  
Cronauer MV, 1997, PROSTATE, V31, P223
[6]   DNA-SEQUENCE OF THE ANDROGEN RECEPTOR IN PROSTATIC TUMOR-CELL LINES AND TISSUE SPECIMENS ASSESSED BY MEANS OF THE POLYMERASE CHAIN-REACTION [J].
CULIG, Z ;
KLOCKER, H ;
EBERLE, J ;
KASPAR, F ;
HOBISCH, A ;
CRONAUER, MV ;
BARTSCH, G .
PROSTATE, 1993, 22 (01) :11-22
[7]  
DAVILA RM, 1993, AM J PATHOL, V142, P547
[8]   HUMAN PERITONEAL MESOTHELIAL CELLS SYNTHESIZE IL-1-ALPHA AND IL-1-BETA [J].
DOUVDEVANI, A ;
RAPOPORT, J ;
KONFORTY, A ;
ARGOV, S ;
OVNAT, A ;
CHAIMOVITZ, C .
KIDNEY INTERNATIONAL, 1994, 46 (04) :993-1001
[9]   Expression of transforming growth factors beta-1, beta 2 and beta 3 in human bladder carcinomas [J].
Eder, IE ;
Stenzl, A ;
Hobisch, A ;
Cronauer, MV ;
Bartsch, G ;
Klocker, H .
BRITISH JOURNAL OF CANCER, 1997, 75 (12) :1753-1760
[10]   Diversity does make a difference: fibroblast growth factor-heparin interactions [J].
Faham, S ;
Linhardt, RJ ;
Rees, DC .
CURRENT OPINION IN STRUCTURAL BIOLOGY, 1998, 8 (05) :578-586