Reduced expression of C1q-mRNA in monocytes from patients with systemic lupus erythematosus.
Inherited C1q deficiency is associated strongly with the development of systemic lupus erythematosus (SLE). The aim of our study was to evaluate the ability of monocytes from SLE patients without inherited C1q deficiency to up-regulate C1q-mRNA upon stimulation. Furthermore, we wanted to elucidate the physiological stimulus for up-regulation of C1q-mRNA. Peripheral blood mononuclear cell (PBMC)-derived monocytes from 10 SLE patients, 10 patients with rheumatoid arthritis (RA) and 10 healthy controls (HC) were stimulated with dexamethasone (DXM), interferon-gamma or both. Additionally, purified monocytes from HC were stimulated with interleukin (IL)-10. C1q-mRNA expression was measured by quantitative reverse transcription-polymerase chain reaction (RT-PCR). C1q protein was detected using the standard alkaline phosphatase/anti-alkaline phosphatase (APAAP) technique. SLE monocytes were significantly less able to up-regulate C1q-mRNA when compared to RA or HC. IL-10 was identified as an important stimulus for C1q synthesis. In SLE patients there is a significant functional impairment of monocytes to synthesize C1q upon stimulation. As C1q is linked to the process of recognition and removal of apoptotic cells, this relative C1q deficiency is likely to contribute to the reduced phagocytosis of apoptotic material observed in SLE and thereby might be a central pathogenetic factor.
Moosig
F
F
University of Schleswig Holstein, Campus Kiel, Kiel, Germany, and Forschungszentrum Borstel, Borstel, Germany.
Damm
F
F
Knorr-Spahr
A
A
Ritgen
M
M
Zeuner
R A
RA
Kneba
M
M
Ernst
M
M
Schröder
J O
JO
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000276:immunology; D002478:Cells, Cultured; D015922:Complement C1q / Q000096:biosynthesis* / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
D000893:Anti-Inflammatory Agents; D012333:RNA, Messenger; D016753:Interleukin-10; D003907:Dexamethasone; D015922:Complement C1q; D007371:Interferon-gamma