Monokines and platelet-derived growth factor modulate prostanoid production in growth arrested, human mesangial cells.
Previous studies have demonstrated considerable prostanoid production by cultured proliferating rat mesangial cells (MC). In this study, human mesangial cells (HMC) were examined during serum-free culture in which the cells were reversibly growth arrested and did not suffer obvious irreversible functional changes. Non-stimulated cells released 2 to 10 pg/24 hr/micrograms cellular protein of PGE2, PGF2 alpha, 6-keto-PGF1 alpha, while TXB2 was not detectable. Stimulation with interleukin-1 beta (IL-1 beta) or tumor necrosis factor alpha (TNF alpha) induced up to 18-fold (IL-1 beta) or up to fourfold (TNF alpha) increases of prostanoid release. Combinations of the two monokines resulted in significant synergistic induction of PGE2 and 6-keto-PGF1 alpha up to 38 times that of control cells. Interleukin-6 (IL-6) and the HMC-mitogen, platelet-derived growth factor-BB (PDGF-BB) only induced marginal increases in HMC prostanoid generation. However, when PDGF-BB or -AB was combined with IL-1 beta or IL-6, prostanoid generation by HMC was synergistically increased up to 222-fold (IL-1 beta) or 12-fold (IL-6) above the control values, with the induction of PGE2 greater than 6-keto-PGF1 alpha greater than PGF2 alpha much greater than TXB2. In the case of IL-1 beta + PDGF-BB the induction of PGE2 release was at least partly due to the synergistic induction of cyclooxygenase activity. These findings demonstrate that both proliferating and reversibly growth arrested HMCs release prostaglandins in response to various inflammatory stimulators and combinations thereof. The findings support the important role of HMC in the regulation of glomerular hemodynamics during inflammatory processes.
Floege
J
J
Department of Nephrology, Medizinische Hochschule Hannover, Federal Republic of Germany.
Topley
N
N
Wessel
K
K
Kaever
V
V
Radeke
H
H
Hoppe
J
J
Kishimoto
T
T
Resch
K
K
D002455:Cell Division; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007378:Interleukins / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis*; D011863:Radioimmunoassay; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D007378:Interleukins; D010982:Platelet-Derived Growth Factor; D011453:Prostaglandins; D014409:Tumor Necrosis Factor-alpha; D011451:Prostaglandin-Endoperoxide Synthases