Lipocortin-l, a 37-kDa member of the annexin family of proteins, origi
nally evoked interest as one of the second messengers for the anti-inf
lammatory actions of glucocorticoids. Studies showed that glucocortico
ids inhibited the proliferation of various cell types and lipocortin-l
mediated growth inhibition of glucocorticoids in a human lung adenoca
rcinoma cell line. The presence of specific lipocortin-1-binding sites
(receptor-like molecules) on monocytic cells has been demonstrated. T
his study was performed to evaluate the effects of hydrocortisone and
recombinant human lipocortin-l on cultured human mesangial cells (CHMC
), and the effects of anti-lipocortin-l antibody on the hydrocortisone
-induced inhibition of CHMC proliferation. The existence of specific b
inding sites for lipocortin-l was also investigated. Lipocortin-l inhi
bited CHMC proliferation in a dose-dependent manner as determined by [
H-3]thymidine uptake and cell count. Growth of CHMC was inhibited to 1
8% of the control in the presence of 5 mu g/ml of lipocortin-l. Simila
r growth-inhibitory activity by lipocortin-l was observed in CHMC acti
vated by platelet-derived growth factor. Hydrocortisone also inhibited
cell proliferation in a dose-dependent manner. One to 5,000 dilution
of anti-lipocortin-l antibody reversed hydrocortisone-induced inhibiti
on of CHMC proliferation partially, whereas concentrations over 1:1,00
0 reversed the inhibition completely. Flow cytometry analysis as well
as indirect immunofluorescent microscopy revealed specific binding sit
es on the surface of CHMC. These results support the hypothesis that c
orticosteroids act by inducing CHMC to synthesize or secrete lipocorti
n-l, and that lipocortin-l generates proliferation-suppressive signal(
s) through specific binding sites on CHMC.