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The bm12 Inducible Model of Systemic Lupus Erythematosus (SLE) in C57BL/6 Mice
Published on: November 1, 2015
Modulation of CR1 transcript in systemic lupus erythematosus (SLE) by IFN-gamma and immune complex
Vaishali Arora1, Abdul Matin Mondal, Rahul Grover
1Department of Biochemistry, All India Institute of Medical Sciences, New Delhi 110029, India.
Insights
Neutrophil CR1 transcript levels are significantly lower in systemic lupus erythematosus (SLE) patients. Interferon-gamma (IFN-gamma) upregulates CR1, while immune complexes downregulate it, highlighting their roles in SLE pathophysiology.
Area of Science:
- Immunology
- Molecular Biology
- Rheumatology
Background:
- Reduced Erythrocyte Complement Receptor 1 (E-CR1) expression is linked to systemic lupus erythematosus (SLE) pathophysiology.
- Neutrophil Complement Receptor 1 (N-CR1) transcript levels and their regulation in SLE are not fully understood.
Purpose of the Study:
- To quantify N-CR1 transcript levels in SLE patients versus healthy individuals.
- To investigate the modulatory effects of interferon-gamma (IFN-gamma), interleukin-4 (IL-4), and immune complexes (IC) on N-CR1 expression in SLE.
Main Methods:
- Real-time RT-PCR was used to measure CR1 transcript levels in neutrophils.
- Neutrophils from 25 untreated active SLE patients and 25 healthy controls were analyzed.
- The impact of IFN-gamma, IL-4, and IC on CR1 transcript levels was assessed.
Main Results:
- SLE patients exhibited significantly lower N-CR1 transcript levels compared to controls.
- IFN-gamma upregulated N-CR1 transcript in both groups, while IC downregulated it in SLE patients.
- IC and IL-4 partially suppressed the IFN-gamma-induced upregulation of N-CR1.
Conclusions:
- N-CR1 transcript is markedly reduced in active SLE.
- IFN-gamma and IC act as positive and negative modulators, respectively, of N-CR1 transcript in SLE.
- These findings provide novel insights into the molecular mechanisms underlying SLE pathogenesis.
Abstract:
Reduced expression of Erythrocyte Complement Receptor 1 (E-CR1) is envisaged to contribute significantly to the pathophysiology of systemic lupus erythematosus (SLE). We determined the levels of CR1 transcript in the neutrophils from 25 untreated patients with active SLE and 25 normal healthy individuals and, studied the effect of interferon-gamma (IFN-gamma), interleukin-4 (IL-4) and immune complexes (IC) on the same. The study revealed a marked decline in the levels of neutrophil CR1 (N-CR1) transcript in the patients with SLE, and differential pattern of IFN-gamma and IL-4 expression in the neutrophils from normals and patients. Opsonized immune complexes down regulated CR1 transcript in patients and IFN-gamma up regulated the same both in normals and patients. Immune complexes suppressed this effect of IFN-gamma. IL-4 also suppressed the effect of IFN-gamma but effect confined only to the normals. This is the first real-time RT-PCR data comparing the neutrophil CR1 expression in normals and patients with SLE and its modulation by IFN-gamma, IL-4 and immune complexes. IFN-gamma and immune complexes, respectively, emerged as the positive and negative modulators of neutrophil CR1 transcript in SLE.
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