High Glucose and Lipopolysaccharide Prime NLRP3 Inflammasome via ROS/TXNIP Pathway in Mesangial Cells.

Abstract

While inflammation is considered a central component in the development in diabetic nephropathy, the mechanism remains unclear. The NLRP3 inflammasome acts as both a sensor and a regulator of the inflammatory response. The NLRP3 inflammasome responds to exogenous and endogenous danger signals, resulting in cleavage of procaspase-1 and activation of cytokines IL-1β, IL-18, and IL-33, ultimately triggering an inflammatory cascade reaction. This study observed the expression of NLRP3 inflammasome signaling stimulated by high glucose, lipopolysaccharide, and reactive oxygen species (ROS) inhibitor N-acetyl-L-cysteine in glomerular mesangial cells, aiming to elucidate the mechanism by which the NLRP3 inflammasome signaling pathway may contribute to diabetic nephropathy. We found that the expression of thioredoxin-interacting protein (TXNIP), NLRP3, and IL-1β was observed by immunohistochemistry in vivo. Simultaneously, the mRNA and protein levels of TXNIP, NLRP3, procaspase-1, and IL-1β were significantly induced by high glucose concentration and lipopolysaccharide in a dose-dependent and time-dependent manner in vitro. This induction by both high glucose and lipopolysaccharide was significantly inhibited by N-acetyl-L-cysteine. Our results firstly reveal that high glucose and lipopolysaccharide activate ROS/TXNIP/ NLRP3/IL-1β inflammasome signaling in glomerular mesangial cells, suggesting a mechanism by which inflammation may contribute to the development of diabetic nephropathy.

• Authors: Hong Feng, Junling Gu, Fang Gou, Wei Huang, Chenlin Gao, Guo Chen, Yang Long, Xueqin Zhou, Maojun Yang, Shuang Liu, Shishi Lü, Qiaoyan Luo, Yong Xu
• Journal: Journal of diabetes research (J Diabetes Res) Vol. 2016 Pg. 6973175 ( 2016) ISSN: 2314-6753 [Electronic] England
• PMID: 26881256 (Publication Type: Journal Article)

Chemical References

• Blood Glucose
• Carrier Proteins
• Cell Cycle Proteins
• Inflammasomes
• Interleukin-1beta
• Lipopolysaccharides
• NLR Family, Pyrin Domain-Containing 3 Protein
• Nlrp3 protein, rat
• Reactive Oxygen Species
• TXNIP protein, rat
• Caspase 1
• Glucose
• Acetylcysteine

Topics

• Acetylcysteine (pharmacology)
• Animals
• Blood Glucose (analysis)
• Carrier Proteins (metabolism)
• Caspase 1 (metabolism)
• Cell Cycle Proteins
• Glucose (metabolism)
• Immunohistochemistry
• Inflammasomes (metabolism)
• Inflammation
• Interleukin-1beta (metabolism)
• Lipopolysaccharides (pharmacology)
• Male
• Mesangial Cells (metabolism)
• NLR Family, Pyrin Domain-Containing 3 Protein (blood)
• Random Allocation
• Rats
• Reactive Oxygen Species
• Signal Transduction