Intermittent High Glucose Exacerbates A-FABP Activation and Inflammatory Response through TLR4-JNK Signaling in THP-1...

Area of Science:

• Endocrinology and Metabolism
• Immunology
• Cell Biology

Background:

• Glucose fluctuations pose risks for diabetes-related vascular diseases, with unclear mechanisms.
• Macrophage activation via Toll-like receptor 4 (TLR4) and c-Jun N-terminal kinase (JNK) signaling is crucial in diabetes progression.

Purpose of the Study:

• To investigate if glucose fluctuation induces macrophage inflammation through TLR4-JNK signaling pathways.
• To explore the role of adipocyte fatty acid-binding protein (A-FABP) in this process.

Main Methods:

• THP-1 cells were exposed to normal, constant high, or intermittent high glucose conditions for 24 hours.
• Key markers including TLR4, phosphorylated JNK (p-JNK), and A-FABP were quantified at mRNA and protein levels.
• Proinflammatory cytokines Tumor Necrosis Factor-alpha (TNF-α) and Interleukin-1 beta (IL-1β) were measured.

Main Results:

• Intermittent high glucose significantly increased TLR4 expression and JNK phosphorylation compared to constant high glucose.
• Both glucose conditions elevated A-FABP expression and release of TNF-α and IL-1β, with a more pronounced effect under intermittent high glucose.
• Inhibiting p-JNK reduced A-FABP and cytokine production without affecting TLR4 expression.

Conclusions:

• Intermittent high glucose potentiates A-FABP activation and inflammatory responses through the TLR4/p-JNK signaling pathway in macrophages.
• Glucose fluctuation has a more detrimental impact on macrophage inflammation in diabetes-related vascular diseases than previously assumed.