Interleukin-1 receptor associated kinase 1 is a potential therapeutic target of anti-inflammatory therapy for systemic lupus erythematosus. (July 2017)

• Record Type: Journal Article
• Authors: Li, Mingfang; Yu, Datang; Ni, Bing; Hao, Fei
• Is Part Of: Molecular immunology. Volume 87(2017:Jul.)
• Page Start: 94
• Page End: 101
• Publication Date: 2017-07
• Subjects: Interleukin-1 receptor associated kinase 1 -- IRAK1 inhibitor -- Nuclear factor-kappa B -- Systemic lupus erythematosus -- Peripheral blood mononuclear cells; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2017.03.018
• Languages: English
• ISSNs: 0161-5890

Abstract

Highlights: Higher levels of IRAK1 activation in splenic mononuclear cells from B6.lpr mice. IRAK1 activation was increased in PBMCs from SLE patients. IRAK-Inh attenuated lupus-related renal damages in B6.lpr mice. IRAK-Inh decreased the IRAK1 and NF-κB activation in PBMCs from SLE patients. IRAK-Inh or IRAK1 shRNA has similar effects on down-regulating NF-κB activation. Abstract: Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease and currently has no effective therapy. The genome-wide analyses indicate that interleukin-1 receptor associated kinase 1 (IRAK1) is associated with the susceptibility of SLE in humans. In the present study, we identified that IRAK1 was overexpressed and hyper-activated in splenic mononuclear cells from B6.MRL-Fas lpr /Nju (B6.lpr) mice and peripheral blood mononuclear cells (PBMCs) from SLE patients. Intraperitoneal treatment with a small molecular inhibitor of IRAK1 (IRAK1/4 inhibitor or IRAK-Inh) significantly mitigated inflammatory responses and renal injury in B6.lpr mice. IRAK-Inh treatment or knockdown of IRAK1 by specific siRNA decreased the relative levels of NF-κBp65 phosphorylation in human PBMCs from SLE patients. Therefore, IRAK1 may be a potential target for anti-inflammatory therapy for SLE and other inflammatory diseases.