Monocyte response to Th1 stimulation and effector function toward human mesangial cells are not impaired in patients with lupus nephritis.
Monocytes/macrophages activated by Th1 stimulation such as interferon-gamma (IFN-gamma) and CD40 ligand (CD40L) infiltrate the kidney and play a critical role in the progression of lupus nephritis (LN). We examined the monocyte response to Th1 stimulation and their effector function toward activating renal resident cells in patients with LN. Following stimulation with IFN-gamma granulocyte macrophage-colony stimulating factor (GM-CSF)/recombinant CD40L the production of tumor necrosis factor-alpha and IL-12 p70 by PBMC was significantly higher in LN patients. In coculture experiments employing activated monocytes and human mesangial cells, there was a trend toward higher monocyte chemoattractant protein-1 production by lupus monocytes compared to normal controls. Basal expression of CD40, ICAM-1, and STAT-1 was significantly higher in monocytes from LN patients, suggesting ongoing activation. Monocyte response to IFN-gamma, as accessed by intercellular adhesion molecule-1 upregulation and phosphorylation of STAT-1, was comparable between the two groups. Thus, in contrast to earlier reports, Th1-dependent monocyte activation is not impaired. In this disease activated monocytes appear to be fully capable of inducing renal injury.
Kuroiwa
Takashi
T
Arthritis and Rheumatism Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA. tkuroiwa@med.gunma-u.ac.jp
Schlimgen
Ryan
R
Illei
Gabor G
GG
Boumpas
Dimitrios T
DT
D000328:Adult; D023201:CD40 Ligand / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D005920:Glomerular Mesangium / Q000187:drug effects / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics; D007371:Interferon-gamma / Q000494:pharmacology; D018664:Interleukin-12 / Q000378:metabolism; D008181:Lupus Nephritis / Q000276:immunology*; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D050794:STAT1 Transcription Factor; D018417:Th1 Cells / Q000276:immunology*; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects; D015854:Up-Regulation
D004268:DNA-Binding Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D023201:CD40 Ligand; D018664:Interleukin-12; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor