Open AccessMitogenic effect of platelet‐derived growth factor in human glomerular mesangial cells: modulation and/or suppression by inflammatory cytokines
Author(s) -
FLOEGE J.,
TOPLEY N.,
HOPPE I.,
BARRETT T. B.,
RESCH K.
Publication year - 1991
Publication title -
clinical & experimental immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 135
eISSN - 1365-2249
pISSN - 0009-9104
DOI - 10.1111/j.1365-2249.1991.tb05819.x
Subject(s) - mesangial cell , platelet derived growth factor receptor , platelet derived growth factor , endocrinology , growth factor , medicine , cytokine , mesangial proliferative glomerulonephritis , tumor necrosis factor alpha , biology , stimulation , alpha (finance) , glomerulonephritis , receptor , kidney , construct validity , nursing , patient satisfaction
SUMMARY Glomerular mesangial cell proliferation constitutes a frequent pathological alteration in glomerulonephritis. In addition to platelet‐derived growth factor (PDGK) inflammatory cytokines such as IL‐1. IL‐6 or tumour necrosis factor‐alpha (TNF‐α) have been proposed to have mitogenic activity for mesangial cells. A model was therefore established in which human mesangial cells (HMC) could be reversibly growth‐arrested for prolonged times in serum‐free medium without suffering irreversible functional or morphological changes. In this model 24 h stimulation with rhPDGF‐BB induced an increase of the 3 H‐thymidine incorporation of 1190.280 (50 ng/ml) %± s.e.m. of medium control. Less growth induction was noted after stimulation with 50 ng ml rhPDGF‐AB (925± I26) or rhPDGF‐AA (575 ± 24%). Northern analysis confirmed the presence of both α and β ‐PDGF receptor subunit mRNA in growth‐arrested HMCs. rhlL‐lα, rhlL‐1 β , rhTNF‐α or rhIL‐6 at various doses and times, despite increasing cellular PGE 2 ‐release, did not induce significant proliferation in HMCs. Inhibition of PGE 2 ‐release did not change the lack ol mitogenicity of lL‐l, TNF‐α or lL‐6. IL‐6 did not alter the mitogenic response of the cells towards PDGF. In contrast, both IL‐lα and lL‐l β (5 ng / ml) induced a delay but not augmentation of the PDGF growth response. This delay could be reversed by the concomitant addition or recombinant IL‐6 or of anti‐lL‐1 antibody but not by inhibition of prostaglandin synthesis. High doses of TNF‐α suppressed PDGF‐induced proliferation. These data suggest that in growth‐arrested HMCs inflammatory cytokines have a growth‐modulating or ‐suppressive rather than (co‐)mitogenic effect while PDGF‐BB and‐AB and to a lesser degree PDGF‐AA are potent mitogens. The findings support the notion that the control of HMC proliferation in pathological situations depends on a complex network of interacting stimuli.