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

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Abstract

Previously we reported disease-specific interaction between interferon-γ (IFN-γ) 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-γ (IFN-γ) and expression of IFN-γ receptor (IFN-γR) 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-γ concentrations in supernatants were evaluated by the enzyme-linked immunosorbent assay (ELISA). Other parts of PBMC pellets were reacted with anti-human IFN-γR monoclonal antibody and FITC-labeled anti-mouse second antibody for analysis of IFN-γR 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-γ or IFN-γR mRNA expression by the semiquantitative RT-PCR method.In vitro IFN-γ 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-γR on macrophages was suppressed in CGN patients. These results suggest that impairment of regulation of the IFN-γ system might be involved in the development of CGN.

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Authors and Affiliations

  1. Department of Internal Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, 259-11, Kanagawa, Japan

    Naohiro Yano, Masayuki Endoh, Raita Naka, Fumio Takemura, Yasuo Nomoto & Hideto Sakai

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  1. Naohiro Yano
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  2. Masayuki Endoh
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  3. Raita Naka
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  4. Fumio Takemura
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  5. Yasuo Nomoto
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  6. Hideto Sakai
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Yano, N., Endoh, M., Naka, R. et al. Altered synthesis of interferon-γ and expression of interferon-γ receptor by peripheral blood mononuclear cells from patients with IgA nephropathy and non-IgA proliferative glomerulonephritis. J Clin Immunol 16, 71–79 (1996). https://doi.org/10.1007/BF01540975

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