Proinflammatory cytokines regulate FcαR expression by human mesangial cells in vitro

Abstract

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 (FcαR) by selected cytokines. Binding of ¹²⁵I-IgA to quiescent human MC showed 2.55 ×10⁵ sites/cell with an affinity (Ka) of 3.2 ×10⁷ 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 pHuFcαR cDNA probe showed time-dependent increases in mRNA expression in stimulated versus control cells. IL-6 and tumour necrosis factor-alpha (TNF-α) had a biphasic effect on the FcαR mRNA level; at 48 h, IL-6 increased steady state mRNA levels about six-fold relative to control, TNF-α increased mRNA four-fold, and interferon-gamma (IFN-γ) induced FcαR mRNA two-fold. By reverse transcriptase-polymerase chain reaction (RT-PCR), the FcαR expressed on human MC appears highly homologous to that expressed by U937 cells. Altered FcαR expression in response to cytokines may influence the pathogenesis of IgAN by affecting deposition and/or clearance of IgA-IC in the mesangium.

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