toll-like receptor 4 Archives

Kuan Yang‘s research focuses on pattern recognition receptors influencing inflammation.

MAIN RESULTS:

NAD+-levels affect the function of toll-like receptor 4.
Serum starvation of cardiac fibroblasts reduces toll-like receptor 4-induced levels of pro-interleukin-1β protein.
CD38 promote NLRP3 activity by increasing cytosolic Ca2+ levels

THESIS DEFENCE:

Thesis: Metabolic Regulation of TLR4 and NLRP3 Activities
Candidate: Kuan Yang
Time: November 25, 2020 at 12:15
Place: Online-based solution, due to the covid-19 situation
Link to university website

SUMMARY:

(1) Inhibition of NAD+ synthesis downregulates the synthesis of toll-like receptor 4-dependent cytokines in human primary monocytes. NAD+-inhibition also inhibits phosphorylation of several proteins involved in the toll-like receptor 4signal pathway.

(2) Serum starvation of cardiac fibroblasts reduces levels of pro-interleukin-1β protein induced by toll-like receptor 4. Tumor necrosis factor, interleukin-6 and inflammasomes proteins are not affected.

To the researchers surprise, pro-interleukin-1β protein levels were increased by mTOR inhibition and degraded by autophagy inhibition. The results suggest that mTOR regulates degradation of pro-interleukin-1β in cardiac fibroblasts through proteasomes but not autophagy.

(3) Interleukin-1β release is attenuated upon NLRP3 inflammasome activation in human monocytes and macrophages treated with CD38 inhibitors. These findings support that CD38 promote NLRP3 activity by increasing cytosolic Ca2+ levels.

REFERENCES:

(1) Yang, K., Lauritzen, K. H., Olsen, M. B., Dahl, T. B., Ranheim, T., Ahmed, M. S., & Sandanger, Ø. (2019). Low Cellular NAD+ Compromises Lipopolysaccharide-Induced Inflammatory Responses via Inhibiting TLR4 Signal Transduction in Human Monocytes. The Journal of Immunology, 203(6), 1598-1608.

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