Interactions of hydrogen peroxide with interleukin-6 and platelet-derived growth factor in determining mesangial cell growth: effect of repeated oxidant stress.
1. This study examined the influence of H2O2, interleukin-6 and platelet-derived growth factor on the proliferation of rat mesangial cells. Mesangial cells were exposed to either a single pulse or three daily pulses of H2O2 (10(-8)-10(-4) mol/l), alone or in combination with interleukin-6 (5 ng/ml) and/or platelet-derived growth factor (10 ng/ml). Proliferation was assessed after 24 h and 72 h of incubation using [3H]thymidine incorporation and cell counts. 2. Although one pulse of H2O2 had no significant effect on mesangial cell proliferation, three daily pulses of 10(-6) mol/l H2O2 resulted in a significant increase in [3H]thymidine incorporation of 31 (52.6, 10.3)% (median and 75th-25th interquartile range) (P < 0.001). Both interleukin-6 and platelet-derived growth factor were also mitogenic to mesangial cells, [3H]thymidine incorporation increasing by 19 (36.7, -6.7)% (P < 0.05) and 53.5 (107, 21.9)% (P < 0.001), respectively. The mitogenic effect of interleukin-6 was enhanced by 10(-6) mol/l H2O2 [49.9 (77.7, 12.3)%] (P < 0.01), whereas the addition of 10(-6) mol/l H2O2 to platelet-derived growth factor resulted in a summated increase in [3H]thymidine incorporation of 82.7 (113, 57.4)% (P < 0.001). Incubation with all three substances simultaneously resulted in down-regulation of growth compared with H2O2 plus platelet-derived growth factor by 55.4 (77.7, 10.3)% (P < 0.05). 3. These findings suggest that reactive oxygen species may play a major role in determining the mesangial cell proliferation that occurs in certain forms of glomerulonephritis, acting either alone or in combination with other growth factors.
D'Souza
R J
RJ
Renal and Clinical Biochemistry Research Laboratories, School of Postgraduate Medicine, University of Keele, North Staffordshire Hospital Centre, Stoke-on-Trent, U.K.
Phillips
H M
HM
Jones
P W
PW
Strange
R C
RC
Aber
G M
GM
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005920:Glomerular Mesangium / Q000166:cytology* / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D008297:Male; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D051381:Rats; D011921:Rats, Inbred WKY; D013997:Time Factors
D015850:Interleukin-6; D010982:Platelet-Derived Growth Factor; D006861:Hydrogen Peroxide