scholarly journals MiR-96-5p alleviates inflammatory responses by targeting NAMPT and regulating the NF-κB pathway in neonatal sepsis

2020 ◽  
Vol 40 (7) ◽  
Author(s):  
Xueli Chen ◽  
Ying Chen ◽  
Li Dai ◽  
Na Wang

Abstract Neonatal septicemia is a serious infectious disease in the neonatal period. MicroRNAs (miRNAs) have been reported to participate in the inflammatory responses in neonatal sepsis. The aim of the present study was to explore the effects and molecular mechanism of miR-96-5p on regulating the inflammatory responses in neonatal sepsis. MiR-96-5p was low expressed while nicotinamide phosphoribosyltransferase (NAMPT) was high expressed in the serum of neonatal septicemia patients. The expression of miR-96-5p was decreased in LPS-induced inflammatory responses. Besides, miR-95-5p relieved LPS-induced inflammatory responses in RAW264.7 cells. NAMPT was demonstrated as a potential target of miR-96-5p, and knockdown of NAMPT reduced inflammatory in RAW264.7 cells stimulated with LPS. Moreover, overexpression of NAMPT reversed the effects of miR-96-5p on LPS-induced inflammatory responses. In addition, miR-96-5p inhibited nuclear factor (NF)-κB signaling pathway in RAW264.7 cells stimulated with LPS. MiR-96-5p alleviated inflammatory responses via targeting NAMPT and inhibiting NF-κB pathway in neonatal sepsis.

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yi Xin ◽  
Qin Yuan ◽  
Chaoqi Liu ◽  
Changcheng Zhang ◽  
Ding Yuan

Abstract It has been demonstrated that Chikusetsusaponin IVa (CsIVa) possesses abundant biological activities. Herein, using LPS to establish acute inflammation model of mouse liver and cell line inflammation model, we investigated whether miR-155/GSK-3β regulated NF-κB signaling pathway, and CsIVa exerted anti-inflammatory effects by regulating miR-155/GSK-3β signaling pathway. Our results showed that LPS induced high expression of miR-155 and miR-155 promoted macrophage activation through GSK-3β. In addition, CsIVa inhibited inflammatory responses in LPS-induced mouse liver and RAW264.7 cells. Furthermore, we demonstrated that CsIVa improved the inflammatory response in LPS-induced RAW264.7 cells by inhibiting miR-155, increasing GSK-3β expression, and inhibiting NF-κB signaling pathway. In conclusion, our study reveals that CsIVa suppresses LPS-triggered immune response by miR-155/GSK-3β-NF-κB signaling pathway.


2018 ◽  
Vol 46 (06) ◽  
pp. 1281-1296 ◽  
Author(s):  
Sang Yun Han ◽  
Young-Su Yi ◽  
Seong-Gu Jeong ◽  
Yo Han Hong ◽  
Kang Jun Choi ◽  
...  

Lilium bulbs have long been used as Chinese traditional medicines to alleviate the symptoms of various human inflammatory diseases. However, mechanisms of Lilium bulb-mediated anti-inflammatory activity and the bioactive components in Lilium bulbs remain unknown. In the present study, the anti-inflammatory activity of Lilium bulbs and the underlying mechanism of action were investigated in macrophages using Lilium bulb ethanol extracts (Lb-EE). In a dose-dependent manner, Lb-EE inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and bone marrow-derived macrophages (BMDMs) without causing significant cytotoxicity. Lb-EE also down-regulated mRNA expression of inflammatory genes in LPS-stimulated RAW264.7 cells, which included inducuble nitric oxide synthase (iNOS), cyclooxygenase-2 (COX2), and tumor necrosis factor-[Formula: see text] (TNF-[Formula: see text]). Furthermore, Lb-EE markedly restored LPS-induced morphological changes in RAW264.7 cells to a normal morphology. HPLC analysis identified quercetin, luteolin, and kaempferol as bioactive components contained in Lb-EE. Mechanistic studies in LPS-stimulated RAW264.7 cells revealed that Lb-EE suppressed MyD88- and TRIF-induced NF-[Formula: see text]B transcriptional activation and the nuclear translocation of NF-[Formula: see text]B transcription factors. Moreover, Lb-EE inhibited IKK[Formula: see text]/[Formula: see text]-induced activation of the NF-[Formula: see text]B signaling pathway and IKK inhibition significantly reduced NO production in LPS-stimulated RAW264.7 cells. Taken together, these results suggest that Lb-EE plays an anti-inflammatory role by targeting IKK[Formula: see text]/[Formula: see text]-mediated activation of the NF-[Formula: see text]B signaling pathway during macrophage-mediated inflammatory responses.


Marine Drugs ◽  
2019 ◽  
Vol 17 (10) ◽  
pp. 552 ◽  
Author(s):  
Jiawen Zheng ◽  
Xiaoxiao Tian ◽  
Wen Zhang ◽  
Pingan Zheng ◽  
Fangfang Huang ◽  
...  

Fucoxanthin (Fx) is a natural extract from marine seaweed that has strong antioxidant activity and a variety of other bioactive effects. This study elucidated the protective mechanism of Fx on alcoholic liver injury. Administration of Fx was associated with lower pathological effects in liver tissue and lower serum marker concentrations for liver damage induced by alcohol. Fx also alleviated oxidative stress, and lowered the level of oxides and inflammation in liver tissue. Results indicate that Fx attenuated alcohol-induced oxidative lesions and inflammatory responses by activating the nuclear factor erythrocyte-2-related factor 2 (Nrf2)-mediated signaling pathway and down-regulating the expression of the toll-like receptor 4 (TLR4)-mediated nuclear factor-kappa B (NF-κB) signaling pathway, respectively. Our findings suggest that Fx can be developed as a potential nutraceutical for preventing alcohol-induced liver injury in the future.


Toxins ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 663 ◽  
Author(s):  
Xi-Chun Wang ◽  
Ya-Fei Zhang ◽  
Li Cao ◽  
Lei Zhu ◽  
Ying-Ying Huang ◽  
...  

Deoxynivalenol (DON) is highly toxic to animals and humans, but pigs are most sensitive to it. The porcine mucosal injury related mechanism of DON is not yet fully clarified. Here, we investigated DON-induced injury in the intestinal tissues of piglet. Thirty weanling piglets [(Duroc × Landrace) × Yorkshire] were randomly divided into three groups according to single factor experimental design (10 piglets each group). Piglets were fed a basal diet in the control group, while low and high dose groups were fed a DON diet (1300 and 2200 μg/kg, respectively) for 60 days. Scanning electron microscopy results indicated that the ultrastructure of intestinal epithelial cells in the DON-treated group was damaged. The distribution and optical density (OD) values of zonula occludens 1 (ZO-1) protein in the intestinal tissues of DON-treated groups were decreased. At higher DON dosage, interleukin (IL)-1β, IL-6, and tumor necrosis factor-α mRNA levels were elevated in the intestinal tissues. The mRNA and protein levels of NF-κB p65, IκB-α, IKKα/β, iNOS, and COX-2 in the small intestinal mucosa were abnormally altered with an increase in DON concentration. These results indicate that DON can persuade intestinal damage and inflammatory responses in piglets via the nuclear factor-κB signaling pathway.


2004 ◽  
Vol 279 (14) ◽  
pp. 13984-13992 ◽  
Author(s):  
Hiroaki Hirotani ◽  
Nathaniel A. Tuohy ◽  
Je-Tae Woo ◽  
Paula H. Stern ◽  
Neil A. Clipstone

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