Abstract
BackgroundThe Nucleotide binding and oligomerization domain-like receptorfamily pyrin domain-containing 3 (NLRP3)-inflammasome plays an important role in various diseases, including a variety of kidney diseases. Naringin exhibits anti-inflammatory and anti-oxidation effects among others, but its specific mechanisms are not clear. We investigated the expression of the NLRP3-inflammasome under high-glucose conditions, assessed the effects of naringin on that process, and further elucidated the role of naringin in the pathogenesis of diabetic kidney disease(DKD).MethodsTo assess the therapeutic potential of naringin and the mechanisms involved, we cultured rat glomerular mesangial cells and grouped them according to different glucose concentrations, different action times, different concentrations of MCC950, and different concentrations of naringin.The cell proliferation was measured by MTT assay. The expression of Interleukin-1β(IL-1β) and Interleukin18 (IL-18) in the cell supernatant were detected by ELISA. The expression and activity of NLPR3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and Caspase-1 were detected by Western Blot.ResultsThe expressions of NLRP3, ASC, caspase-1, IL-1β, and IL-18 in rat glomerular mesangial cells were significantly higher in the high glucose (HG) group than in the control normal glucose (NG) group and exhibited time-dependence activity. The expression levels of NLRP3, caspase-1, IL-1β, and IL-18 in different treatment groups were significantly lower compared with the HG group after 48 h of MCC950 pre-treatment (p < 0.05). Pre-treatment with naringin produced the same results. Naringin also inhibited the proliferation of cells.ConclusionsThe NLRP3-inflammasome potentially plays a role in the process of activation and inflammation of glomerular mesangial cells as induced by high-glucose conditions. Naringin inhibited the proliferation of cells that were induced by high glucose. Further, it reduced the expression of inflammatory factors that are mediated by NLRP3 through the NLRP3-caspase-1-IL-1β/IL-18 signaling pathway, which makes naringin a potentially novel treatment for DKD disease.
Highlights
The Nucleotide binding and oligomerization domain-like receptorfamily pyrin domain-containing 3 (NLRP3)-inflammasome plays an important role in various diseases, including a variety of kidney diseases
Effect of glucose concentrations on the proliferation of rat glomerular mesangial cells at different time points To investigate the effect of high glucose concentrations on rat glomerular mesangial cells over time, we performed experiments with varying concentrations of glucose and sampled at varying time points
Expression of NLRP3, a caspase recruitment domain (ASC), caspase-1, IL-1β, and IL-18 in each group at different time points We further explored whether high glucose can induce activation of inflammasomes in rat glomerular mesangial cells by analyzing the expression of NLRP3, ASC, and caspase-1
Summary
The Nucleotide binding and oligomerization domain-like receptorfamily pyrin domain-containing 3 (NLRP3)-inflammasome plays an important role in various diseases, including a variety of kidney diseases. We investigated the expression of the NLRP3-inflammasome under high-glucose conditions, assessed the effects of naringin on that process, and further elucidated the role of naringin in the pathogenesis of diabetic kidney disease(DKD). The NLRP3 inflammasome is a member of the nucleotide-binding domain and leucine-rich repeat containing family, and is composed of NLRP3, apoptosis-associated specklike protein containing a CARD (ASC), and procaspase-1. It senses endogenous and exogenous danger signals, including lipopolysaccharides (LPS) and high glucose levels (HG), and it cleaves procaspase-1 and activates the cytokines IL-1β, IL-18, and IL-33 that trigger the inflammatory cascade [14,15,16]
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