Deregulated NLRP3 and NLRP1 Inflammasomes and Their Correlations with Disease Activity in Systemic Lupus Erythematosus

Journal of Rheumatology - Tập 41 Số 3 - Trang 444-452 - 2014
Qingrui Yang1, Chengcheng Yu2, Zhaowen Yang3, Qing Wei4,5,6,7,8,9,10,11,12, Kun Mu4,5,6,7,8,9,10,11,12, Ying Zhang4,5,6,7,8,9,10,11,12, Wei Zhao4,5,6,7,8,9,10,11,12, Xiaofeng Wang4,5,6,7,8,9,10,11,12, Wanwan Huai4,5,6,7,8,9,10,11,12, Lihui Han4,5,6,7,8,9,10,11,12
1From the Department of Immunology, Shandong University School of Medicine
2 the Provincial Hospital Affiliated to Shandong University
3 and the Department of Pathology, Shandong University School of Medicine, Jinan, China.
4Department of Immunology, Shandong University School of Medicine, 44 Wenhua Xi Road, Jinan 250012, China
5Department of Immunology, Shandong University School of Medicine. Dr. Qingrui
6Department of Immunology, Shandong University School of Medicine; X. Wang, MD,
7Department of Immunology, Shandong University School of Medicine; Z. Yang, MD,
8From the Department of Immunology, Shandong University School of Medicine; the Provincial Hospital Affiliated to Shandong University; and the Department of Pathology, Shandong University School of Medicine, Jinan, China.
9Provincial Hospital Affiliated to Shandong University
10Provincial Hospital Affiliated to Shandong University; Q. Wei, MS, Department of Immunology,
11Shandong University School of Medicine; K. Mu, MD, PhD, Department of Pathology,
12Shandong University School of Medicine; Y. Zhang, BS;

Tóm tắt

Objective.NOD-like receptor family, pyrin domain containing 3 and 1 (NLRP3 and NLRP1) inflammasomes are molecular platforms that sense the damage or danger signals of cells. We investigated whether NLRP3/NLRP1 inflammasomes are involved in the pathogenesis and progression of systemic lupus erythematosus (SLE).Methods.Expressions of inflammasome components at the mRNA and protein levels in the peripheral blood mononuclear cells (PBMC) from patients with SLE and healthy controls were investigated by quantitative real-time transcription PCR and Western blot, respectively. Correlations between NLRP3/NLRP1 inflammasome components’ expression and clinical disease progression were investigated. Expressions of NLRP3/NLRP1 inflammasomes before and after treatment in the patients with SLE were also analyzed and compared.Results.Our data showed that expressions of NLRP3/NLRP1 inflammasomes were significantly downregulated in PBMC from patients with SLE compared with PBMC from healthy controls. Further, expressions of NLRP3/NLRP1 inflammasomes were negatively correlated with the SLE Disease Activity Index, and regular glucocorticoid treatment significantly corrected this deregulation of these inflammasomes. Further analysis showed that type I interferon (IFN) level was significantly negatively correlated with expression of NLRP3/NLRP1 inflammasomes, which indicated that enhanced IFN-I level in patients with SLE was responsible, at least to a great degree, for the deregulation of inflammasomes.Conclusion.These results indicated deregulation of NLRP3/NLRP1 inflammasomes in patients with SLE, and suggested an important role for inflammasomes in the pathogenesis and progression of SLE.

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Tài liệu tham khảo

10.1016/j.immuni.2006.02.004

10.4049/jimmunol.1002720

10.1369/jhc.6A7101.2006

10.1002/art.1780350606

10.1016/j.chom.2010.11.007

10.1097/BOR.0b013e3283562c3e

10.1136/ard.2004.033753

10.1016/j.smim.2011.01.009

10.1089/jir.2011.0071

10.1002/art.23035

10.1016/j.clim.2009.08.014

10.1002/art.22044

10.1002/art.21890

10.3109/08916934.2011.637532

10.1016/j.molmed.2010.11.001

10.1084/jem.20100050

10.1002/ibd.21478

10.1016/j.immuni.2010.03.003

10.1016/j.it.2011.02.002

10.1111/j.1600-065X.2008.00730.x

10.1038/nature08100

10.1016/j.immuni.2011.02.006

10.1126/scisignal.2002767

10.1371/journal.pone.0027040

10.1038/ni.2237

10.1016/j.cell.2010.01.040

10.1038/nature10759

10.1038/ni.1703

10.1016/j.immuni.2012.05.030

Zhang, 2004, Activation-induced cell death in T cells and autoimmunity, Cell Mol Immunol, 1, 186