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Aberrant Low Expression of A20 in Tumor Necrosis Factor-α-stimulated SLE Monocytes Mediates Sustained NF-κB Inflammatory Response.
- Source :
- Immunological Investigations; Jul2015, Vol. 44 Issue 5, p497-508, 12p
- Publication Year :
- 2015
-
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. [ABSTRACT FROM AUTHOR]
- Subjects :
- ABERRANT crypt foci
GENE expression
TUMORS
NECROSIS
MONOCYTES
Subjects
Details
- Language :
- English
- ISSN :
- 08820139
- Volume :
- 44
- Issue :
- 5
- Database :
- Complementary Index
- Journal :
- Immunological Investigations
- Publication Type :
- Academic Journal
- Accession number :
- 108697905
- Full Text :
- https://doi.org/10.3109/08820139.2015.1037957