Macrophage Activation by Fructose Prevented by Antioxidant Sufficiency Blocks TXNIP Conversion of M2 into M1

What we were talking about recently.  Inflamasome activation converts anti inflammatory macrophage 2 into pro inflammatory macrophage 1.  This macrophage activation is the putative cause of asthma and diabetes.  Blocking the NLRP3 inflamasome prevents cell damage and death.  Sepsis and ischemia reperfusion injury activate the inflamasome.  Too much fructose leading to too much oxidative stress causes damaging pro inflammatory TXNIP to be increased.  Verapamil can directly inhibit TXNIP but then oxidative stress directly damages cells.  The solution is safer antioxidants.

Sepsis is an increased oxidative stress, NLRP3, increased TXNIP condition.  Studies show a 30% reduction of mortality with Vitamin C in animal models.

Generally endogenous antioxidants  superoxide dismutase and glutathione are superior to direct antioxidants like vitamin c.

This should prevent loss of beta cell function and progression of diabetes.  This should prevent or decrease asthma exacerbation teiggered by infections that promote oxidative stress.

I prefer to use sulforaphane from broccoli sprouts and spermidine from wheat germ to achieve increased antioxidant, increased energy production and inhibition of toxic inflammatory TXNIP.

http://link.springer.com/article/10.1007/s10753-017-0542-4

Quercetin and Ascorbic Acid Suppress Fructose-Induced NLRP3 Inflammasome Activation by Blocking Intracellular Shuttling of TXNIP in Human Macrophage Cell Lines

22 March 2017

The aim of this study was to identify the role of thioredoxin-interacting protein (TXNIP) and its interaction with antioxidants in the activation of the fructose-induced NOD-like receptor protein 3 (NLRP3) inflammasome in human macrophages. The study was performed with U937 and THP-1 macrophage cell lines. Total reactive oxygen species (ROS) were measured by flow cytometry. Interleukin-1β (IL-1β), IL-18, NLRP3, TXNIP, and caspase-1 protein expression was detected using western blotting. Quantitative real-time polymerase chain reaction was used to detect IL-1β, IL-18, and caspase-1 gene expression. Intracellular shuttling of TXNIP was assessed by immunofluorescent staining with MitoTracker Red. Increased production of ROS and expression of IL-1β, IL-18, and caspase-1 genes and proteins were observed in U937 and THP-1 cells incubated with fructose and were effectively inhibited by quercetin and ascorbic acid. Intracellular shuttling of TXNIP from the nucleus into the mitochondria was detected under stimulation with fructose, which was also attenuated by antioxidants quercetin and ascorbic acid but not butylated hydroxyanisole. Treatment of macrophages with fructose promoted the association between TXNIP and NLRP3 in the cytosol, sequentially resulting in the activation of the NLRP3 inflammasome. This study revealed that intracellular TXNIP protein is a critical regulator of activation of the fructose-induced NLRP3 inflammasome, which can be effectively blocked by the antioxidants quercetin and ascorbic acid.