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Reactivity of mesangial cells with aberrantly glycosylated IgA: modulation by angiotensin converting enzyme inhibitors
Author(s) -
Amore Alessandro,
Cirina Paola,
Chiesa Monica,
Coppo Rosanna
Publication year - 2002
Publication title -
nephrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 61
eISSN - 1440-1797
pISSN - 1320-5358
DOI - 10.1046/j.1440-1797.7.s3.7.x
Subject(s) - enalapril , endocrinology , in vitro , medicine , intracellular , angiotensin ii , nephropathy , nitric oxide , enzyme , chemistry , angiotensin converting enzyme , biochemistry , receptor , blood pressure , diabetes mellitus
SUMMARY:The aim of the present study was to evaluate the modulating effect of angiotensin‐converting enzyme inhibitors (ACE‐I) on the reactivity of mesangial cells (MC) challenged with aberrantly glycosylated IgA. In vitro prepared desialylated and degalactosylated IgA (deSia/deGal IgA) were incubated with cultured MC in the presence or absence of enalapril 10–100 ng/mL. DeSia/deGal IgA significantly depressed the MC proliferation rate, simultaneously enhancing the apoptotic rate. A negative control on vascular endothelial growth factor synthesis was found which was mediated by enhanced inducible macrophage‐type nitric oxide synthase activity. The coincubation with enalapril 100 ng/mL significantly reversed these effects. Aberrantly glycosylated IgA induced clear expression of α‐smooth muscle cell actin in MC, suggesting an acquisition of miofibroblast‐like phenotype. The ACE‐I, again, significantly inhibited this effect. In order to evaluate the intracellular mechanisms activated by ACE‐I, the authors aimed to investigate the modulating activity of aberrantly glycosylated IgA and ACE‐I on the nuclear factor (NF)‐κB transcriptional factor system. In MC treated with aberrantly glycosylated IgA, the activation of the NF‐κB/IκB complex leading to translocation of NF‐κB into the nucleus, was detected. The phenomenon was significantly blunted by the co‐incubation with ACE‐I. The present study indicates that ACE‐I may limit the effects on MC of the altered glycosylation of circulating IgA molecules in patients with IgA nephropathy via the inhibition of the transcriptional factor NF‐κB. These in vitro results might add further support to the possible benefit of ACE‐I therapy in progressive IgA nephropathy.