scholarly journals MiR-223 improves intestinal inflammation through inhibiting the IL-6/STAT3 signaling pathway in dextran sodium sulfate-induced experimental colitis

2020 ◽  
Author(s):  
Juanjuan Zhang ◽  
Chenyang Wang ◽  
Zhen Guo ◽  
Binlin Da ◽  
Weiming Zhu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Sodium Sulfate ◽  
Quantitative Polymerase Chain Reaction ◽  
Negative Control ◽  
Dextran Sodium Sulfate ◽  
Enzyme Linked Immunosorbent Assay ◽  
Colonic Inflammation ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Tnf Α

Abstract Background: The pathogenesis of inflammatory bowel disease (IBD) has not yet been clarified and is closely related to several proinflammatory factors. MicroRNA-233 (miR-223) might be involved in the development of IBD; however, the mechanism underlying its pathogenesis is unclear. In this study, we attempted to determine the role of miR-223 in dextran sodium sulfate (DSS)-induced colitis and explore the involvement of the IL-6/STAT3 pathway in the development of intestinal mucosal inflammation.Methods: Male C57BL/6 mice were divided into six groups: control (WT) group, DSS group, DSS+miR-223 agomir (DSS+A) group, DSS+miR-223 agomir negative control (DSS+A+NC) group, DSS+miR-223 antagomir (DSS+AN) group and DSS+miR-223 antagomir negative control (DSS+AN+NC) group. Body weight, stool consistency, fecal blood and the disease activity index (DAI) score were recorded daily. The length of each colon was measured, and colonic inflammation was evaluated with hematoxylin and eosin (H&E) staining and histopathological scoring. The expression of myeloperoxidase (MPO), TNF-α, IL-6, IL-10 and IL-17 in the colonic tissues was measured by Enzyme-linked Immunosorbent Assay (ELISA) and real-time quantitative polymerase chain reaction (RT-qPCR). The mRNA expression of gp130, Bcl-2 and Bcl-xl in the colon was measured using RT-qPCR. The colonic levels of STAT3 and p-STAT3 were determined by Western blotting.Results: MiR-223 expression in the terminal ileum and colon was increased in the DSS group compared with the WT group. Colitis symptoms were significantly alleviated in the DSS+A group and exacerbated in the DSS+AN group after administration of the miR-223 agomir and antagomir, respectively. MPO, TNF-α, IL-6 and IL-17 were decreased and IL-10 was increased in the DSS+A group, but these changes were reversed in the DSS+AN group. Gp130 mRNA, p-STAT3, Bcl-2 and Bcl-xl in the colon declined in the DSS+A group, but these levels increased in the DSS+AN group.Conclusion: The upregulation of miR-223 by agomir administration alleviated colonic inflammation in a DSS-induced colitis model, which was likely mediated by inhibiting the production of proinflammatory cytokines via the IL-6/STAT3 signaling pathway. These findings provide evidence that miR-223 might have potential therapeutic implications in IBD.

scholarly journals Mechanism of TCONS_00147848 regulating apoptosis of nasal mucosa cells and alleviating allergic rhinitis through FOSL2-mediated JAK/STAT3 signaling pathway

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Haiyun Huang ◽  
Yu Ren ◽  
Hongyu Liang ◽  
Xiaojia Liu ◽  
Jisangmo Nan ◽  
...  
Keyword(s):  
Allergic Rhinitis ◽  
Allergic Reaction ◽  
Signaling Pathway ◽  
Nasal Mucosa ◽  
Rna Binding ◽  
Cell Counting ◽  
Enzyme Linked Immunosorbent Assay ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Tnf Α

AbstractThis study was conducted to explore the roles and related mechanisms of lncRNA-TCONS_00147848 (TCONS_00147848) in nasal mucosa cell apoptosis and allergic rhinitis (AR). AR mice were sensitized with ovalbumin (OVA), with the TCONS_00147848 interference lentiviral vector (TCONS_00147848 shRNA) and FOSL2 overexpressing lentiviral vectors (pCDH-FOSL2) constructed respectively. NC shRNA, TCONS_00147848 shRNA and TCONS_00147848 shRNA + pCDH-FOSL2 were transfected into AR mice and mice with TNF-α induced nasal mucosa cells. The allergic reaction symptoms were evaluated by scoring. And in this study, we used Hematoxylin–Eosin (HE) staining and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) to detect the histological changes of nasal mucosa and apoptosis of nasal mucosa epithelial cells in mice, cell counting kit-8 (CCK-8) assay, Transwell and annexin V/PI to detect proliferation, migration and apoptosis of nasal mucosa cells of mice, respectively, enzyme-linked immunosorbent assay (ELISA) to detect the expression of inflammatory factors, qRT-PCR to detect TCONS_00147848 expression, Western blot assay to detect the expressions of FOSL2, JAK-2, STAT3, p-STAT3, BAX and BCL-2, RNA-binding protein immunoprecipitation (RIP) assay, RNA pull down assay and Co-immunoprecipitation (CoIP) assay to identify TCONS_00147848 targeting FOSL2. All these findings above reveal that knocking down TCONS_00147848 can reduce the allergic reaction symptom score of AR mice and the inflammatory reaction. The expression of IgE, IL-4, IL-5, IL-10, IL-9, IFN-γ and TNF-α in serum decreased. The expression of FOSL2, JAK-2, p-STAT3 and BAX in nasal mucosa and nasal mucosa cells of mice decreased as well, but BCL-2 expression increased. In addition, koncking down TCONS_00147848 can also inhibit the apoptosis of TNF-α induced nasal mucosa cells in mice and promote cell proliferation and migration. However, FOSL2 overexpression neutralized the effect of TCONS_00147848 shRNA. In nasal mucosa cells of mice, TCONS_00147848 can target FOSL2, interacting with STAT3. Inhibition of TCONS_00147848 can regulate JAK/STAT3 signaling pathway and reduce inflammatory response in AR mice.

scholarly journals EFFECT OF LUNASIN-RICH SOYBEAN EXTRACT UPON TNF-α EXPRESSION ON COLONIC EPITHELIAL CELLS OF MICE INDUCED BY AZOXYMETHANE/DEXTRAN SODIUM SULFATE

2019 ◽  
pp. 12-16
Author(s):  
KUSMARDI KUSMARDI ◽  
RENATA TAMARA ◽  
ARI ESTUNINGTYAS ◽  
ARYO TEDJO
Keyword(s):  
Epithelial Cells ◽  
Sodium Sulfate ◽  
Distal Colon ◽  
Positive Control ◽  
Negative Control ◽  
Dextran Sodium Sulfate ◽  
Colon Tissue ◽  
Colonic Epithelial Cells ◽  
Tnf Α ◽  
Soybean Extract

Objective: Colorectal cancer (CRC) contributes to 9.7% of all cancer, and its pathogenesis is related to chronic inflammation. However, current cancer therapy options are lacking, and peptide in food has become popular among researchers because it is cheap, easy to get, has a low toxicity, and is a promising cancer-preventing agent. This research aimed to investigate whether lunasin from soybeans can reduce the expression of pro-inflammatory cytokine TNF-α in colonic epithelial cells. Methods: Thirty Swiss Webster mice were randomly allocated to six groups. One group was normal, and in five groups, carcinogenesis was induced using azoxymethane (AOM) and dextran sodium sulfate (DSS). The mice were then given nothing (negative control), aspirin (positive control), and lunasin-rich soybean extract (LSE) in three different doses (250, 300, and 350 mg/kgBW) for four weeks. Distal colon tissue was immunohistochemically stained and then observed under a light microscope with 400X magnification to count epithelial cells, based on their color. The index was calculated using optical density scores. Results: LSE was shown to decrease the expression of tumor necrosis factor (TNF)-α. This decrease was statistically significant between the negative control and a dose of 300 mg/kgBW (p=0.016) and 350 mg/kgBW (p=0.009), yet it was not significant with a dose of 250 mg/kgBW (p=0.754). Conclusion: a dose of 300 mg/kgBW or higher of LSE can reduce the expression of TNF-α.

Protective effects of tryptophan-catabolizing Lactobacillus plantarum KLDS 1.0386 against dextran sodium sulfate-induced colitis in mice

2020 ◽  
Vol 11 (12) ◽  
pp. 10736-10747
Author(s):  
Jialu Shi ◽  
Peng Du ◽  
Qinggang Xie ◽  
Nana Wang ◽  
Huizhen Li ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Acetic Acid ◽  
Gut Microbiota ◽  
Lactobacillus Plantarum ◽  
Sodium Sulfate ◽  
Dextran Sodium Sulfate ◽  
Protective Effects ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Indole 3 Acetic Acid

L. plantarum KLDS 1.0386 combined with tryptophan alleviates ulcerative colitis (UC) induced by dextran sodium sulfate (DSS) by increasing the level of indole-3-acetic acid (IAA), stimulating the AHR/IL-22/STAT3 signaling pathway and regulating gut microbiota in mice.

scholarly journals The intervention of S1PR1/STAT3 signaling pathway by inhibiting the expression of STAT3 attenuates the valvular damage due to rheumatic heart disease

2020 ◽  
Author(s):  
Shenglin Xian ◽  
Ang Chen ◽  
Yunjiao Wu ◽  
Hong Wen ◽  
Chuanghong Lu ◽  
...  
Keyword(s):  
Heart Disease ◽  
Signaling Pathway ◽  
Rheumatic Heart Disease ◽  
Orphan Receptor ◽  
Enzyme Linked Immunosorbent Assay ◽  
T Helper 17 ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Sphingosine 1 Phosphate ◽  
Rheumatic Heart

Abstract Background Rheumatic heart disease (RHD) is a social health problem that affects many patients every year, but its pathogenesis is still unclear. Recent studies have found that the sphingosine 1-phosphate receptor 1 (S1PR1)/signal transducer and activator of transcription 3 (STAT3) signaling pathway is activated during the development of valvular damage caused by RHD. STAT3 plays an important role in the differentiation of CD4 + T cells into T helper 17 (Th17) cells, and Th17 cell-related cytokines are involved in the development of RHD. In this work, we investigated whether altering the S1PR1/STAT3 signaling pathway by inhibiting the expression of STAT3 attenuates valvular damage due to RHD. Methods Inactivated Group A streptococci (GAS) and complete Freund’s adjuvant (CFA) were used to establish the RHD rat model. STAT3-small interfering RNA (STAT3-siRNA) was used to directly inhibit the expression of STAT3 in the heart. Histological examination was used to evaluate the degree of inflammation and fibrosis in valve tissues. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry were used to detect the levels of interleukin (IL)-6 and IL-17 in serum and valve tissue. Reverse transcription-quantitative PCR (RT-qPCR) was used to detect the mRNA expression of S1PR1 and STAT3. Western blotting (WB) and immunohistochemistry were used to detect the protein expression of S1PR1, STAT3, phosphorylated (p-) STAT3, retinoic acid-related orphan receptor gamma T (RORγt). Results The expression of S1PR1 in valve tissues of RHD model rats was decreased. The degree of valvular inflammation and fibrosis of RHD model rats was increased. The levels of IL-6 and IL-17 in valves and serum of RHD model rats were increased as well as an increase of p-STAT3 in valve tissues. Inhibition of STAT3 by STAT3-siRNA decreased STAT3 expression and reduced the total amount of p-STAT3, resulting in decreased expression of IL-6, IL-17 and RORγt in valves and serum and reduced valvular inflammatory response and fibrosis. Conclusions These results suggest that inhibiting the expression of STAT3 in the heart may reduce the valvular damage caused by rheumatic heart disease.

Inhibition of Stat3 signaling pathway decreases TNF-α-induced autophagy in cementoblasts

2018 ◽  
Vol 374 (3) ◽  
pp. 567-575 ◽  
Author(s):  
Leilei Wang ◽  
Yunlong Wang ◽  
Mingyuan Du ◽  
Zhijian Liu ◽  
Zhengguo Cao ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Tnf Α
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