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, 103)% (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.
Production by cultured human monocytes of mesangial cell proliferation factor(s) differing from interleukin-1 and interleukin-6