Sodium butyrate attenuate hyperglycemia-induced inflammatory response and renal injury in diabetic mice.

The activation of the monocyte-macrophage system and the damage to the renal and pancreatic tissue are common complications in patients with diabetes induced by hyper-glycemia. This study aimed to evaluate the effect and mechanism of butyrate (NaB), a metabolite of intestinal flora, on inhibiting the inflammatory response of human monocyte-macrophages (THP-1 cells) induced by high glucose and the damage of pancreatic and renal tissue in diabetic mice. The results showed that high concentration glucose significantly up-regulated the expressions of IL-1ß, TNF-α, and NLRP3 in THP-1 cells and mouse spleen, and that NaB could inhibit the overexpression of those genes. The abundance of Beclin-1, LC3B and reactive oxygen species (ROS) in THP-1 cells is increased due to the high glucose concentration, and NaB can inhibit the genes responsible for upregulating the expression. In diabetic mice, vacuolar degeneration of renal tubules was observed. Then we observed that some of the epithelial cells of the renal tubules were exfoliated and some formed tubules. NaB could alleviate these pathological lesions, but NaB cannot alleviate pancreatic injury. Our results indicated that NaB could be used for the prevention and adjuvant treatment of diabetic kidney injury.

Short-Chain Fatty Acids Weaken Ox-LDL-Induced Cell Inflammatory Injury by Inhibiting the NLRP3/Caspase-1 Pathway and Affecting Cellular Metabolism in THP-1 Cells.

Short-chain fatty acids (SCFAs) are important anti-inflammatory metabolites of intestinal flora. Oxidized low-density lipoprotein (ox-LDL)-induced macrophage activation is critical for the formation of atherosclerosis plaque. However, the association between SCFAs and ox-LDL-induced macrophage activation with respect to the formation of atherosclerosis plaque has not yet been elucidated. The present study investigated whether SCFAs (sodium acetate, sodium propionate, and sodium butyrate) can affect ox-LDL-induced macrophage activation and potential signaling pathways via regulation of the expression of the NLRP3/Caspase-1 pathway. Using human monocyte-macrophage (THP-1) cells as a model system, it was observed that ox-LDL not only induced cell inflammatory injury but also activated the NLRP3/Caspase-1 pathway. The exogenous supplementation of three SCFAs could significantly inhibit cell inflammatory injury induced by ox-LDL. Moreover, three SCFAs decreased the expression of IL-1ß and TNF-α via the inactivation of the NLRP3/Caspase-1 pathway induced by ox-LDL. Furthermore, three SCFAs affected cellular metabolism in ox-LDL-induced macrophages, as detected by untargeted metabolomics analysis. The results of the present study indicated that three SCFAs inhibited ox-LDL-induced cell inflammatory injury by blocking the NLRP3/Caspase-1 pathway, thereby improving cellular metabolism. These findings may provide novel insights into the role of SCFA intervention in the progression of atherosclerotic plaque formation.

Lactobacillus rhamnosus TR08 Improves Dyslipidemia in Mice Fed with a High Fat Diet by Regulating the Intestinal Microbiota, Reducing Systemic Inflammatory Response, and Promoting Sphingomholipid Metabolism.

Dysbiosis is a crucial manifestation of dyslipidemia; however, oral supplementation of probiotic modulates the intestinal commensal composition. The protective mechanism of probiotics against hyperlipidemia is still under investigation. To elucidate the hypolipidemic effect of Lactobacillus rhamnosus TR08 through the analysis of gut microbiota and lipid metabolomics, we investigated changes in gut microbiota and lipid metabolomic phenotypes in mice by real time quantitative PCR and untargeted metabolomics analysis. High fat diet-induced dyslipidemia mice were orally administered with TR08 for 8 weeks. The proinflammatory cytokines (interleukin-2 and interferon-γ) levels in spleen and aortic wall injury in the mice fed with a high-fat diet were inhibited after treatment with TR08 at 1 × 108 CFU per day per mouse. TR08 also reshaped the gut microbiota with increases of the relative abundances of Bifidobacterium and Bacteroides, reduced the abundance of the pro-pathogen bacterial Enterococcus, increased the serum level of short chain fatty acids (SCFAs) contents, and promoted sphingomholipid metabolic pathway. The results indicated that TR08 could improve the intestinal microbiota of mice to increase the production of SCFAs, and then play the anti-inflammation induced by hyperlipidemia and reduce the inflammatory injury of blood vessel wall. Therefore, TR08 can potentially be used as a hypolipidemic effect probiotic in further interventions.

[Mycoplasma pneumoniae toxin of community-acquired respiratory distress syndrome (CARDS) promotes autophagy of THP-1 cells and activates NLRP3 inflammasomes].

Objective To study the mechanism of community-acquired respiratory distress syndrome (CARDS) toxin of Mycoplasma pneumoniae (Mp) inducing THP-1 cell autophagy and the activation of pyrin domain containing the nucleotide-binding oligomerization domain-like receptor family 3 (NLRP3). Methods The recombinant CARDS (rCARDS) Mp toxin was obtained by Escherichia coli expression system, and THP-1 cells were treated with the toxin at the concentrations of 5 and 10 µg/mL for 20, 40 minutes, 1, 2 and 3 hours. The expression of autophagy-related proteins beclin-1, LC3II and P62 of THP-1 cells were determined by Western blot; the gene expression of NLRP3, caspase-1 and interleukin 1ß (IL-1ß) were detected by real-time quantitative PCR; and the level of reactive oxygen species (ROS) of THP-1 cells was tested by DCFH-DA staining. Results Compared with the control group, when treated with rCARDS toxin for 1 hour, the expression of beclin-1, LC3 and P62 significant increased. When treated with rCARDS toxin for 2 and 3 hours, the expression of beclin-1, LC3 and P62 significant decreased. When treated with rCARDS toxin for 20 and 40 minutes, the NLRP3 gene expression had no significant difference between the groups treated with the concentration of 5 and 10 µg/mL rCARDS toxin. NLRP3 gene expression in the groups treated with rCARDS toxin was higher than that in the control group in the whole experiment. When treated with rCARDS toxin for 1 hour and 2 hours, the NLRP3 gene expression of the 10 µg/mL group was significant higher than that in the 5 µg/mL group. When treated with rCARDS toxin for 3 hours, the NLRP3 gene expression of the 10 µg/mL group and 5 µg/mL group was lower than that in the groups treated for 2 hours. When treated with rCARDS toxin for 40 minutes, 1 hour and 2 hours, the caspase-1 mRNA expression of rCARDS toxin groups was higher than that in the control group. When treated for 40 minutes, 1, 2 and 3 hours, the caspase-1 gene expression of the 10 µg/mL group was significantly higher than that in the 5 µg/mL group. Compared to the control group, when treated with rCARDS toxin for 20 and 40 minutes, IL-1ß gene expression had no significant difference. When the time prolonged to 1 hour and 3 hours, the levels of IL-1ß mRNA expression and ROS had a significant increase in a dose-dependent manner in all groups. Conclusion CARDS Mp toxin can activate NLRP3 inflammasomes and induce cell autophagy in THP-1 cells.