title: Aberrant Low Expression of A20 in Tumor Necrosis Factor-α-stimulated SLE Monocytes Mediates Sustained NF-κB Inflammatory Response.
abstract: The aberrantly activated monocytes and nuclear factor-kappaB (NF-κB) pathway contribute to the pathogenesis of systemic lupus erythematosus (SLE), and the aberrantly activated NF-κB is associated with defects in the anti-inflammatory A20 in SLE. However, whether SLE monocytes express A20 and whether the A20 expression under sustained proinflammatory stimulation is altered to contribute to the uncontrolled NF-κB inflammatory response are unclear. In this study, we found that the freshly isolated monocytes from SLE patients and healthy controls did not differ in expression levels of IL-1β, IκBα and A20. After TNF-α stimulation for 48 h, the monocytes from both groups expressed higher levels of IL-1β and IκBα than the monocytes without TNF-α treatment. Although the increased levels of NF-κB were observed in the nucleus of both the SLE and control monocytes after 24 h of TNF-α stimulation, the enhancement in SLE monocytes was significantly more robust than in the control monocytes. In addition, while the p-IκBα level in healthy monocytes was increased, the p-IκBα level in SLE monocytes was slightly decreased after TNF-α stimulation. Interestingly, after TNF-α treatment, the A20 expression in SLE monocytes was not markedly altered compared with the untreated SLE monocytes; moreover, the SLE monocytes expressed significantly lower A20 than healthy monocytes with TNF-α treatment at each time point. Results in this study demonstrate that TNF-α activates a significant NF-κB inflammatory response in SLE monocytes, which is at least partially mediated by the aberrantly low expression of A20 upon TNF-α stimulation, contributing to the prolonged inflammatory response in SLE.
authors.affiliation: Department of Dermatology, Southwest Hospital, Third Military Medical University , Chongqing , China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Shi
authors.forename: Tian
authors.initials: T
authors.lastname: Qian
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Fangru
authors.initials: F
authors.lastname: Chen
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Fei
authors.initials: F
authors.lastname: Hao
mesh_terms: D002469:Cell Separation; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007249:Inflammation; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D004268:DNA-Binding Proteins; D053583:Interleukin-1beta; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins; D014409:Tumor Necrosis Factor-alpha; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3
keywords: A20; inflammatory response; monocyte; nuclear factor-kappaB; systemic lupus erythematosus; tumor necrosis factor-alpha