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Abnormal production of pro- and anti-inflammatory cytokines by lupus monocytes in response to apoptotic cells.

PloS one (2011-03-23)
Sangeeta Sule, Antony Rosen, Michelle Petri, Ehtisham Akhter, Felipe Andrade
ABSTRACT

Monocytes are a key component of the innate immune system involved in the regulation of the adaptive immune response. Previous studies have focused on apoptotic cell clearance abnormalities in systemic lupus erythematosus (SLE) monocytes. However, whether SLE monocytes might express unique patterns of cytokine secretion in response to apoptotic cells is still unknown. Here, we used monocytes from healthy controls and SLE patients to evaluate the production of TNF-α and TGF-β in response to apoptotic cells. Upon recognition of apoptotic material, monocytes from healthy controls showed prominent TGF-β secretion (mean ± SD: 824.6±144.3 pg/ml) and minimal TNF-α production (mean ± SD: 32.6±2.1 pg/ml). In contrast, monocytes from SLE patients had prominent TNF-α production (mean ± SD: 302.2±337.5 pg/ml) and diminished TGF-β secretion (mean ± SD: 685.9±615.9 pg/ml), a difference that was statistically significant compared to normal monocytes (p≤10(-6) for TNF-α secretion, and p = 0.0031 for TGF-β, respectively). Interestingly, the unique cytokine response by SLE monocytes was independent of their phagocytic clearance efficiency, opsonizing autoantibodies and disease activity. We further showed that nucleic acids from apoptotic cells play important role in the induction of TNF-α by lupus monocytes. Together, these observations suggest that, in addition to potential clearance defects, monocytes from SLE patients have an abnormal balance in the secretion of anti- and pro-inflammatory cytokines in response to apoptotic cells. Since the abnormal cytokine response to apoptotic material in SLE is not related to disease activity and opsonizing autoantibodies, it is possible that this response might be an intrinsic property of lupus monocytes. The studies focus attention on toll-like receptors (TLRs) and their downstream pathways as mediators of this response.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Human Serum, from human male AB plasma, USA origin, sterile-filtered
Sigma-Aldrich
Human Serum, Heat Inactivated, from human male AB plasma, USA origin, sterile-filtered
Sigma-Aldrich
Human Serum, (from male AB clotted whole blood), USA origin, sterile-filtered
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Human Serum, Heat Inactivated (from male AB clotted whole blood), USA origin, sterile-filtered
Sigma-Aldrich
Human Serum, from platelet poor human plasma, sterile-filtered, (mycoplasma tested, virus tested)