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- Title
Intermittent High Glucose Exacerbates A-FABP Activation and Inflammatory Response through TLR4-JNK Signaling in THP-1 Cells.
- Authors
Li, Hui; Luo, Han-Ying; Liu, Qing; Xiao, Yang; Tang, Lin; Zhong, Feng; Huang, Gan; Xu, Jun-Mei; Xu, Ai-Min; Zhou, Zhi-Guang; Dai, Ru-Ping
- Abstract
<bold>Background: </bold>Glucose fluctuation confers additional risks on diabetes-related vascular diseases, but the underlying mechanisms are unknown. Macrophage activation mediated by TLR4-JNK signaling plays an important role during the progress of diabetes. In the present study, we hypothesize that glucose fluctuation results in macrophage inflammation through TLR4-JNK signaling pathways.<bold>Methods: </bold>THP-1 cells were treated with normal glucose (5 mM), constant high glucose (25 mM), and intermittent high glucose (rotation per 6 h in 5 mM or 25 mM) for 24 h. The mRNA and protein expression levels of TLR4, p-JNK, and adipocyte fatty acid-binding protein (A-FABP) were determined, and the proinflammatory cytokines TNF-α and IL-1β were quantified.<bold>Results: </bold>In constant high glucose, TLR4 expression and JNK phosphorylation levels increased, and this effect was more pronounced in intermittent high glucose. Accordingly, the expression of A-FABP and the release of the proinflammatory cytokines TNF-α and IL-1β also increased in response to constant high glucose, an effect that also was more evident in intermittent high glucose. The inhibition of p-JNK by SP600125 did not attenuate TLR4 expression, but totally inhibited both A-FABP expression and the production of the proinflammatory cytokines TNF-α and IL-1β in both constant and intermittent high glucose.<bold>Conclusions: </bold>Intermittent high glucose potentiates A-FABP activation and inflammatory responses via TLR4/p-JNK signaling in THP-1 cells. These findings suggest a more detrimental impact of glucose fluctuation on macrophage inflammation in diabetes-related vascular diseases than thus far generally assumed.
- Subjects
GLUCOSE; VASCULAR diseases; MACROPHAGE activation; DIABETES; MESSENGER RNA
- Publication
Journal of Immunology Research, 2018, p1
- ISSN
2314-8861
- Publication type
journal article
- DOI
10.1155/2018/1319272