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Interleukin‐10 differentially modulates MHC class II expression by mesangial cells and macrophages in vitro and in vivo
Author(s) -
Steven J. Chadban,
Gregory H Tesch,
Rita Foti,
Hui Y. Lan,
Robert C. Atkins,
David J. Nikolic-Paterson
Publication year - 1998
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.1998.00487.x
Subject(s) - mhc class ii , major histocompatibility complex , mhc class i , biology , microbiology and biotechnology , flow cytometry , mesangial cell , immunology , immune system , endocrinology , kidney
Inhibition of major histocompatibility complex (MHC) class II expression by macrophages is the primary mechanism by which interleukin‐10 (IL‐10) exerts imm_une suppression. Little, however, is known of the effects of IL‐10 on other types of cells which can be induced to express MHC class II during an inflammatory response. We therefore studied the effects of IL‐10 treatment on the expression of MHC class II molecules in a rat model of imm_unologically induced glomerulonephritis. MHC class II mRNA levels in whole kidney were increased in saline‐treated (control) animals with glomerulonephritis (2·6‐fold increase versus normal, P =0·028) and this was partially inhibited by treatment with IL‐10 ( P =NS). Double imm_unostaining of tissue sections was used to compare MHC class II expression by infiltrating macrophages and resident glomerular cells. IL‐10 treatment reduced the proportion of glomerular macrophages which expressed detectable MHC class II (70% reduction, P =0·03). In contrast, IL‐10 treatment was associated with an increase in the number of resident glomerular cells expressing MHC class II, particularly within mesangial areas. Therefore, the effects of IL‐10 on macrophages and mesangial cells were compared in vitro . IL‐10 reduced constitutive MHC class II mRNA and cell surface expression by peritoneal macrophages. In contrast, IFN‐γ‐stimulated mesangial cells (1097 cell line) cultured with IL‐10 for 24 hr showed increased MHC class II mRNA (26% increase) and surface expression (72% increase in percentage MHC II + by flow cytometry, P =0·04) as compared with cells stimulated with IFN‐γ alone. IL‐10 also directly up‐regulated expression of ICAM‐1 by 1097 cells. In conclusion, IL‐10 was found to have contrasting effects on the production and cell surface expression of MHC class II molecules by mesangial cells and by macrophages, both in vitro and in vivo . The implications of these findings for IL‐10‐mediated imm_unosuppression are discussed.