Transforming growth factor-beta synthesis by human peritoneal mesothelial cells. Induction by interleukin-1. |
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| Authors: | F. A. Offner H. Feichtinger S. Stadlmann P. Obrist C. Marth P. Klingler B. Grage M. Schmahl C. Knabbe |
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| Affiliation: | Department of Pathology, University of Innsbruck, Austria. |
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| Abstract: | ![]()
Peritoneal mesothelial cells are uniquely located to regulate cellular events in the peritoneal cavity and are a potentially important source for various cytokines. The present study was designed to elucidate the capacity of human peritoneal mesothelial cells (HPMCs) to synthesize and secrete the transforming growth factor (TGF)-beta isoforms 1, 2, and 3 and to characterize their regulation by inflammatory cytokines. HPMCs constitutively released appreciable amounts of TGF-beta 1 and low amounts of TGF-beta 2 as detected by specific immunoassays. TGF-beta 1 levels secreted within 48 hours (45 +/- 8.9 pg/10(5) cells) were 60-fold higher than TGF-beta 2 levels (0.9 +/- 0.1 pg/10(5) cells), respectively. Treatment of HPMCs with interleukin (IL)-1 beta (10 ng/ml) resulted in a significant increase of both TGF-beta 1 (mean, 5-fold; P < 0.001) and TGF-beta 2 (mean, 6-fold; P < 0.01) generation. After 48 hours of IL-1 beta treatment the levels were 185 +/- 17.1 pg/10(5) cells for TGF-beta 1 and 5.3 +/- 1.5 pg/10(5) cells for TGF-beta 2, respectively. Neither tumor necrosis factor (TNF)-alpha nor interferon (IFN)-gamma (both 10 ng/ml) affected TGF-beta 1 or TGF-beta 2 synthesis by HPMCs. TGF-beta 3 could not be detected in any of the supernatant media. Stimulation of HPMCs with IL-1 beta increased steady-state levels of TGF-beta 1- and TGF-beta 2-specific mRNA. Western blot analysis of supernatants revealed the presence of an immunoreactive band at 25 kd. Indirect competition assays confirmed receptor-binding activity of HPMC-derived TGF-beta. Appreciable amounts of TGF-beta were present in a bioactive form. Our results demonstrate that HPMCs synthesize the TGF-beta isoforms 1 and 2 and that the levels of mRNA and protein release can be up-regulated by the proinflammatory cytokine IL-1 beta. |
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