Altered synthesis of interferon-? and expression of interferon-? receptor by peripheral blood mononuclear cells from patients with IgA nephropathy and non-IgA proliferative glomerulonephritis

Abstract

Previously we reported disease-specific interaction between interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) in patients with IgA nephropathy (IgAN), suggesting the existence of unusual T cell behavior in this disease. In the present study, we investigated characteristic synthesis of interferon-gamma (IFN-gamma) and expression of IFN-gamma receptor (IFN-gamma R) in the peripheral blood mononuclear cells (PBMC) from patients with IgAN and other chronic proliferative glomerulonephritis (PGN). Heparinized peripheral blood samples were obtained from 38 patients with chronic mesangial proliferative glomerulonephritis (CGN; including 24 with IgA nephropathy) and 20 healthy controls. PBMC were isolated by gradient centrifugation and fragments were cultured in Iscove's modified Dulbecco's medium (IMDM) supplemented with 10% fetal calf serum (FCS) for 72 hr. IFN-gamma concentrations in supernatants were evaluated by the enzyme-linked immunosorbent assay (ELISA). Other parts of PBMC pellets were reacted with anti-human IFN-gamma R monoclonal antibody and FITC-labeled anti-mouse second antibody for analysis of IFN-gamma R expression on these cells by FACScan. The remaining PBMC were fractionated into CD4+ T cells, CD8+ T cells, B cells, NK, cells and macrophages using the MACS cell sorting system. The isolated cells were evaluated for IFN-gamma or IFN-gamma R mRNA expression by the semiquantitative RT-PCR method. In vitro IFN-gamma synthesis was enhanced in patients with CGN, and NK cells were revealed to be responsible for such enhancement. On the other hand, the expression of IFN-gamma R on macrophages was suppressed in CGN patients. These results suggest that impairment of regulation of the IFN-gamma system might be involved in the development of CGN.

Down-regulation of Fcα receptors on blood cells of IgA nephropathy patients: Evidence for a negative regulatory role of serum IgA

“…One of the factors that could be involved in the genesis of altered Fc␣R sialylation on blood cells is interferon-␥, as it can induce Fc␣R expression on U937 cells with altered mobility on SDS-PAGE [26]. It is noteworthy that elevated levels of interferon-␥ are indeed found in plasma of IgAN patients [39].…”

Production of Interferon-?by Tonsillar Mononuclear Cells in IgA Nephropathy Patients

“…High levels of serum IFN-k in IgAN patients were also found (10). Additionally, IFN-k production in 6i6o and in 6itro by PBMC in IgAN patients was higher than that with other glomerulonephritis (11).…”

“…Production of interferon-k (IFN-k), a representative Th1 cytokine, has been reported to be associated with the development and progression of IgAN (9)(10)(11). Production of IFN-k in 6itro by peripheral blood mononuclear cells (PBMC) from patients with IgAN was higher than that from control PBMC (9).…”

Cytokine Expression Pattern in Benign Prostatic Hyperplasia Infiltrating T Cells and Impact of Lymphocytic Infiltration on Cytokine mRNA Profile in Prostatic Tissue

“…Resulting PCR fragments were separated by electrophoresis on 1.5% agarose gels (Bio-Rad Laboratories) in combination with a 100-bp size marker (Advanced Biotechnologies, Surrey, United Kingdom) and visualized and photographed after ethidium bromide staining under UV transillumination. cDNA of prostatic cells (normal prostatic SC, BPH-SC, BPH-EC, BPH-T, and CaP cells) and of positive control cells, ie, peripheral blood lymphocytes either unstimulated or stimulated with PHA M (Gibco BRL), was tested for lymphokine receptor mRNA expression using primer specific for the following: IFN-␥R ␣-chain (Yano et al, 1996); IL-2R ␥-chain (Meazza et al, 1998); IL-2R ␤-chain (Meazza et al, 1998); IL-2R ␣-chain (Clontech, Palo Alto California); IL-4R ␣-chain (Clontech); IL-13R ␣-chain (Ogata et al, 1998); and ␤-actin (Clontech).…”