Sodium Houttuyfonate Ameliorates DSS-induced Colitis Aggravated by Candida albicans through Dectin-1/NF-κB/miR-32-5p/NFKBIZ Axis Based on Intestinal microRNA Profiling
》》Journal:Inflammation.
》》相关产品:Acetylcysteine (N-acetylcysteine) (SJ-MX0166) 和 Z-VAD(OH)-FMK (SJ-BP0022)
》》产品引用描述:
》》Abstract
Our previous research indicated that Sodium houttuyfonate (SH) can effectively ameliorate dextran sulfate sodium (DSS)-induced colitis exacerbated by Candida albicans. However, the underlying protective mechanism of SH remains unclear. Therefore, in this study, a mice colitis model was infected with C. albicans, and the total colonic miRNAs were assessed. Furthermore, the differentially expressed miRNAs were enriched, clustered, and analyzed. Moreover, based on the dual luciferase analysis of NFKBIZ modulation by miR-32-5p, the in vitro and in vivo therapeutic effects of SH on inflammatory response, fungal burden, oxidative stress, and apoptosis were assessed at transcriptional and translational levels in the presence of agonist and antagonist. A total of 1157 miRNAs were identified, 84 of which were differentially expressed. Furthermore, qRT-PCR validated that SH treatment improved 17 differentially expressed miRNAs with > fourfold upregulation or > sixfold downregulation. Similar to most differentially altered miRNA, C. albicans significantly increased Dectin-1, NF-κB, TNF-α, IL-1β, IL-17A, and decreased miR-32-5p which negatively targeted NFKBIZ. In addition, SH treatment reduced inflammatory response and fungal burden in a colitis model with C. albicans infection. Further analyses indicated that in C. albicans infected Caco2 cells, SH inhibited fungal growth, oxidative stress, and apoptosis by increasing Dectin-1, NF-κB, NFKBIZ, TNF-α, IL-1β, IL-17A, and decreasing miR-32-5p. Therefore, SH can ameliorate the severity of colitis aggravated by C. albicans via the Dectin-1/NF-κB/miR-32-5p/NFKBIZ axis.
》》部分文献数据展示:
Fig. 10:SH aggravated ROS in Caco2. Expression of ROS in Caco2 was detected by (A) fuorescence microscope (200×) and (B) fow
cytometry. The fungal cells (3×105 CFU/mL) were pre-incubated with SH (32 μg/mL) overnight prior to being introduced to Caco2
cells which were processed with 50 μM NAC for 2 h in advance.
Fig. 11:SH aggravated apoptosis of Caco2. The apoptosis level of Caco2 was detected by (A) fuorescence microscope (200×) and
(B) fow cytometry. The fungal cells (3× 105 CFU/mL) were pre-incubated with SH (32 μg/mL) overnight prior to being introduced
to Caco2 cells which were processed with 5 mM z-VAD-FMK for 2 h in advance. The mixture of Caco2 and C. albicans is processed
as described in Fig. 7. Caco2 was screened by a human anti-CD44 antibody and the quantifcation of the apoptosis is shown in Figure
B (right, lower). Bar=50 μm.