Proinflammatory cytokines regulate Fc alphaR expression by human mesangial cells in vitro.
IgA nephropathy (IgAN) is defined by the predominant deposition of IgA immune complexes (IC) in the glomerular mesangium. Interaction between IgA immune complexes and mesangial cells (MC) could be a linchpin for the genesis of IgAN. We studied the modulation of MC expression of IgA receptors (Fc alphaR) by selected cytokines. Binding of 125I-IgA to quiescent human MC showed 2.55 x 10(5) sites/cell with an affinity (Ka) of 3.2 x 10(7) M(-1). Addition of selected recombinant cytokines had no significant influence on Ka, but increased the number of sites/cell relative to unstimulated cells. Northern hybridization using the pHuFc alphaR cDNA probe showed time-dependent increases in mRNA expression in stimulated versus control cells. IL-6 and tumour necrosis factor-alpha (TNF-alpha) had a biphasic effect on the Fc alphaR mRNA level; at 48 h, IL-6 increased steady state mRNA levels about six-fold relative to control, TNF-alpha increased mRNA four-fold, and interferon-gamma (IFN-gamma) induced Fc alphaR mRNA two-fold. By reverse transcriptase-polymerase chain reaction (RT-PCR), the Fc alphaR expressed on human MC appears highly homologous to that expressed by U937 cells. Altered Fc alphaR expression in response to cytokines may influence the pathogenesis of IgAN by affecting deposition and/or clearance of IgA-IC in the mesangium.
Bagheri
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Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
Chintalacharuvu
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SR
Emancipator
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SN
D000818:Animals; D015703:Antigens, CD / Q000235:genetics*; D016207:Cytokines / Q000494:pharmacology*; D005920:Glomerular Mesangium / Q000166:cytology*; D005922:Glomerulonephritis, IGA / Q000378:metabolism; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D051379:Mice; D011485:Protein Binding; D012333:RNA, Messenger / Q000032:analysis; D011961:Receptors, Fc / Q000235:genetics*; D017423:Sequence Analysis, RNA; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015703:Antigens, CD; D016207:Cytokines; C036832:Fc(alpha) receptor; D007070:Immunoglobulin A; D015850:Interleukin-6; D012333:RNA, Messenger; D011961:Receptors, Fc; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma