scholarly journals TREM1 Blockade Ameliorates Lipopolysaccharide-Induced Acute Intestinal Dysfunction through Inhibiting Intestinal Apoptosis and Inflammation Response

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Lijuan Shen ◽  
Yonghua Zhou ◽  
Xiping Wu ◽  
Yuewen Sun ◽  
Tao Xiao ◽  
...  
Keyword(s):  
Western Blot ◽  
High Mobility ◽  
Male Rats ◽  
Saline Injection ◽  
Inflammation Response ◽  
Injection Model ◽  
Tnf Α ◽  
Epithelial Cell Apoptosis ◽  
Apoptosis And Inflammation

Objective. The lipopolysaccharide- (LPS-) induced acute intestinal dysfunction model has been widely applied in recent years. Here, our aim was to investigate the effect of triggering receptor expressed on myeloid cells-1 (TREM1) inhibitor in LPS-induced acute intestinal dysfunction. Methods. Male rats were randomly assigned into normal (saline injection), model (LPS and saline injection), and LP17 (LPS and LP17 (a synthetic TREM1 inhibitor) injection) groups. The levels of intestinal TREM1 expression were evaluated by immunohistochemistry and western blot. Intestinal permeability and apoptosis were separately assessed by the lactulose/mannitol (L/M) ratio and TUNEL assay. The levels of soluble TREM1 (sTREM1), TNF-α, IL-6, and IL-1β were measured in the plasma and intestinal tissues by ELISA. The expression levels of NF-κB, high-mobility group box 1 (HMGB1), and toll-like receptor 4 (TLR-4) were measured with RT-qPCR and western blot. After transfection with si-TREM1 in LPS-induced intestinal epithelium-6 (IEC-6) cells, p-p65 and p-IκBα levels were detected by western blot. Results. LP17-mediated TREM1 inhibition alleviated the intestine tissue damage in rats with LPS-induced acute intestinal dysfunction. LP17 attenuated the LPS-induced increase in sTREM1, TNF-α, IL-6, and IL-1β levels in the plasma and intestinal tissues. Furthermore, intestine permeability and epithelial cell apoptosis were ameliorated by LP17. LP17 attenuated the LPS-induced increase in the expression of TREM1, HMGB1, TLR-4, and NF-κB in the intestine tissues. In vitro, TREM1 knockdown inactivated the NF-κB signaling in LPS-induced IEC-6 cells. Conclusion. LP17 could ameliorate LPS-induced acute intestinal dysfunction, which was associated with inhibition of intestinal apoptosis and inflammation response.

scholarly journals Protective Effect of Opuntia dillenii Haw Fruit against Lead Acetate-Induced Hepatotoxicity: In Vitro and In Vivo Studies

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Reza Shirazinia ◽  
Ali Akbar Golabchifar ◽  
Vafa Baradaran Rahimi ◽  
Abbas Jamshidian ◽  
Alireza Samzadeh-Kermani ◽  
...  
Keyword(s):  
Cell Viability ◽  
Lead Acetate ◽  
Male Rats ◽  
Tnf Α ◽  
Wide Range ◽  
Hepatoprotective Effects ◽  
Anti Inflammatory ◽  
Opuntia Dillenii

Lead is one of the most common environmental contaminants in the Earth’s crust, which induces a wide range of humans biochemical changes. Previous studies showed that Opuntia dillenii (OD) fruit possesses several antioxidant and anti-inflammatory properties. The present study evaluates OD fruit hydroalcoholic extract (OHAE) hepatoprotective effects against lead acetate- (Pb-) induced toxicity in both animal and cellular models. Male rats were grouped as follows: control, Pb (25 mg/kg/d i.p.), and groups 3 and 4 received OHAE at 100 and 200 mg/kg/d + Pb (25 mg/kg/d i.p.), for ten days of the experiment. Thereafter, we evaluated the levels of alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), catalase (CAT) activity and malondialdehyde (MDA) in serum, and liver histopathology. Additionally, the cell study was also done using the HepG2 cell line for measuring the direct effects of the extract on cell viability, oxidative stress MDA, and glutathione (GSH) and inflammation tumor necrosis factor-α (TNF-α) following the Pb-induced cytotoxicity. Pb significantly increased the serum levels of ALT, AST, ALP, and MDA and liver histopathological scores but notably decreased CAT activity compared to the control group ( p < 0.001 for all cases). OHAE (100 and 200 mg/kg) significantly reduced the levels of serum liver enzyme activities and MDA as well as histopathological scores while it significantly increased CAT activity compared to the Pb group ( p < 0.001 –0.05 for all cases). OHAE (20, 40, and 80 μg/ml) concentration dependently and significantly reduced the levels of MDA and TNF-α, while it increased the levels of GSH and cell viability in comparison to the Pb group ( p < 0.001 –0.05 for all cases). These data suggest that OHAE may have hepatoprotective effects against Pb-induced liver toxicity both in vitro and in vivo by its antioxidant and anti-inflammatory activities.

scholarly journals A Novel Lactic Acid Bacteria Mixture: Macrophage-Targeted Prophylactic Intervention in Colorectal Cancer Management

2020 ◽  
Vol 8 (3) ◽  
pp. 387
Author(s):  
Petra Hradicka ◽  
Jane Beal ◽  
Monika Kassayova ◽  
Andrew Foey ◽  
Vlasta Demeckova
Keyword(s):  
Colorectal Cancer ◽  
Male Rats ◽  
Cancer Management ◽  
Immune Parameters ◽  
Chemically Induced ◽  
Tnf Α ◽  
Vitro Model ◽  
Macrophage Subsets

Colorectal cancer (CRC) is one of the most common forms of cancer. Its onset from chronic inflammation is widely accepted. Moreover, dysbiosis plays an undeniable role, thus the use of probiotics in CRC has been suggested. They exhibit both anti- and pro-inflammatory properties and restore balance in the microbiota. The aim of this study was to investigate the immunomodulatory properties of six lactobacilli with probiotic features in an in vitro model of macrophage-like cells and to test these pooled probiotics for their anti-tumour properties in a chemically induced CRC model using Wistar male rats. Upon co-culture of M1- and M2-like macrophages with lactobacilli, cytokine release (TNF-α, IL-1β, IL-18, IL-23) and phagocytic activity using fluorescent-labelled bacteria were tested. The effects of orally administered probiotics on basic cancer and immune parameters and cytokine concentration (TNF-α, IL-1β, IL-18) in colon tumours were studied. Tested lactobacilli exhibited both pro- and anti-inflammatory properties in in vitro conditions. In vivo study showed that the administration of probiotics was able to decrease multiplicity, volume and total tumour numbers, restore colon length (p < 0.05) and increase IL-18 production (p < 0.05) in tumour tissue. These data indicate both an immunomodulatory effect of probiotics on distinct macrophage subsets and a protective effect against chemically-induced CRC.

scholarly journals Long noncoding RNA MAPKAPK5-AS1 promoted lipopolysaccharide-induced inflammatory damage in the myocardium by sponging microRNA-124-3p/E2F3

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Weiwei Chen ◽  
Guangyuan Gao ◽  
Mengjie Yan ◽  
Ming Yu ◽  
Kaiyao Shi ◽  
...  
Keyword(s):  
Cell Apoptosis ◽  
Noncoding Rna ◽  
Myocardial Dysfunction ◽  
H9c2 Cell ◽  
Rat Cardiomyocytes ◽  
Inflammation Response ◽  
Inflammatory Damage ◽  
Apoptosis And Inflammation

Abstract Background Myocardial dysfunction caused by sepsis (SIMD) leads to high mortality in critically ill patients. We investigated the function and mechanism of long non-coding RNA MAPKAPK5-AS1 (lncRNA MAPKAPK-AS1) on lipopolysaccharide (LPS)-induced inflammation response in vivo and in vitro. Method Male SD rats were utilized for in vivo experiments. Rat cardiomyocytes (H9C2) were employed for in vitro experiments. Western blotting was employed to measure protein expression, and RT-PCR was performed to measure mRNA expression of inflammation factors. TUNEL and flow cytometry were carried out to evulate cell apoptosis. Result The results showed that the expression of MAPKAPK5-AS1 was increased, while the expression of miR-124-3p was decreased in the inflammatory damage induced by LPS in vivo and in vitro. Knockdown of MAPKAPK5-AS1 reduced LPS-induced cell apoptosis and inflammation response, while overexpression of miR-124-3p weakened the effects of MAPKAPK5-AS1 knockdown on LPS-induced cell apoptosis and inflammation response. Moreover, miR-124-3p was identified as a downstream miRNA of MAPKAPK5-AS1, and E2F3 was a target of miR-214-3p. MAPKAPK5-AS1 knockdown increased the expression of miR-124-3p, while miR-124-3p overexpression reduced the expression of MAPKAPK5-AS1. In addition, miR-124-3p was found to downregulate E2F3 expression in H9C2 cells. Conclusion MAPKAPK5-AS1/miR-124-3p/E2F3 axis regulates LPS-related H9C2 cell apoptosis and inflammatory response.

scholarly journals Glycoproteins From Rabdosia japonica var. glaucocalyx Regulate Macrophage Polarization and Alleviate Lipopolysaccharide-Induced Acute Lung Injury in Mice via TLR4/NF-κB Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
An-qi Ren ◽  
Hui-jun Wang ◽  
Hai-yan Zhu ◽  
Guan Ye ◽  
Kun Li ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Western Blot ◽  
Mononuclear Cells ◽  
Macrophage Polarization ◽  
Enzyme Linked Immunosorbent Assay ◽  
Protective Effects ◽  
Proinflammatory Mediators ◽  
Tnf Α

Background and Aims:Rabdosia japonica var. glaucocalyx is a traditional Chinese medicine (TCM) for various inflammatory diseases. This present work aimed to investigate the protective effects of R. japonica var. glaucocalyx glycoproteins on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and the potential mechanism.Methods: Glycoproteins (XPS) were isolated from R. japonica var. glaucocalyx, and homogeneous glycoprotein (XPS5-1) was purified from XPS. ANA-1 cells were used to observe the effect of glycoproteins on the secretion of inflammatory mediators by enzyme-linked immunosorbent assay (ELISA). Flow cytometry assay, immunofluorescence assay, and Western blot analysis were performed to detect macrophage polarization in vitro. The ALI model was induced by LPS via intratracheal instillation, and XPS (20, 40, and 80 mg/kg) was administered intragastrically 2 h later. The mechanisms of XPS against ALI were investigated by Western blot, ELISA, and immunohistochemistry.Results:In vitro, XPS and XPS5-1 downregulated LPS-induced proinflammatory mediators production including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, and nitric oxide (NO) and upregulated LPS-induced IL-10 secretion. The LPS-stimulated macrophage polarization was also modulated from M1 to M2. In vivo, XPS maintained pulmonary histology with significantly reducing protein concentration and numbers of mononuclear cells in bronchoalveolar lavage fluid (BALF). The level of IL-10 in BALF was upregulated by XPS treatment. The level of cytokines including TNF-α, IL-1β, and IL-6 was downregulated. XPS also decreased infiltration of macrophages and polymorphonuclear leukocytes (PMNs) in lung. XPS suppressed the expression of key proteins in the TLR4/NF-κB signal pathway.Conclusion: XPS was demonstrated to be a potential agent for treating ALI. Our findings might provide evidence supporting the traditional application of R. japonica var. glaucocalyx in inflammation-linked diseases.

scholarly journals Morinda officinalis oligosaccharides alleviate depressive-like behaviors in post-stroke rats via suppressing NLRP3 inflammasome to inhibit hippocampal inflammation

2021 ◽  
Author(s):  
Zhifang Li ◽  
Hexiang Xu ◽  
Yi Xu ◽  
Guanfeng Lu ◽  
Qiwei Peng ◽  
...  
Keyword(s):  
Western Blot ◽  
Nlrp3 Inflammasome ◽  
Inflammasome Activation ◽  
Inflammation Response ◽  
Post Stroke ◽  
Pyrin Domain ◽  
Bv2 Cells ◽  
Post Stroke Depression ◽  
Depressive Episodes

Abstract Background: Morinda officinalis oligosaccharides (MOOs) is a traditional Chinese medicine extracted from plant Morinda officinalis roots. It has been used to treat mild and moderate depressive episodes. In the present study, we investigated whether MOOs can ameliorate depressive-like behaviors in post-stroke depression (PSD) rats and further discussed its mechanism by suppressing microglial NLRP3 inflammasome activation to inhibit hippocampal inflammation.Methods: Behaviors tests were performed to evaluate the effect of MOOs on depressive-like behaviors in PSD rats. The effects of MOOs on the expression of IL-18, IL-1β and nucleotide-binding domain leucine-rich repeat family pyrin domain containing 3 (NLRP3) inflammasome were measured in both PSD rats and lipopolysaccharide (LPS)+adenosine triphosphate (ATP) stimulated BV2 cells by reverse transcription polymerase chain reaction (RT-PCR), immunofluorescence and Western blot analysis. Adeno-associated virus (AAV) were injected into hippocampus to downregulate NLRP3 inflammasome expression. The detailed molecular mechanism underlying the effects of MOOs was analyzed by Western blot and immunofluorescence.Results: MOOs can alleviate depressive-like behaviors in PSD rats. PSD rats showed increased expression of IL-18, IL-1β and NLRP3 inflammasome in the ischemic hippocampus, while MOOs compromised the elevation. NLRP3 downregulation ameliorated depressive-like behaviors and hippocampal inflammation response in PSD rats. Moreover, we found that NLRP3 is mainly expressed on microglia. In vitro, MOOs effectively inhibited the expression of IL-18, IL-1β and NLRP3 inflammasome in LPS+ ATP treated BV2 cells. We further showed that modulation of NLRP3 inflammasome by MOOs was associated with IκB/NF‐κB p65 signaling pathway.Conclusion: Overall, our study revealed the antidepressive effect of MOOs on PSD rats through modulation of microglial NLRP3 inflammasome. We also provide a novel insight into hippocampal inflammation response in PSD pathology and put forward NLRP3 inflammasome as a potential therapeutic target for PSD.

scholarly journals Quercetin inhibits TNF-α induced HUVECs apoptosis and inflammation via downregulating NF-kB and AP-1 signaling pathway in vitro

Medicine ◽  
2020 ◽  
Vol 99 (38) ◽  
pp. e22241
Author(s):  
Tielong Chen ◽  
Xudong Zhang ◽  
Guangli Zhu ◽  
Hongfei Liu ◽  
Jinru Chen ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Tnf Α ◽  
Apoptosis And Inflammation

scholarly journals Effects of Neuromedin S on the Proliferation of Splenic Lymphocytes and the Cytokine Secretion by Pulmonary Alveolar Macrophages in Pigs in vitro

2016 ◽  
Vol 19 (3) ◽  
pp. 485-494 ◽  
Author(s):  
R. Lin ◽  
Q. Wang ◽  
B. Qi ◽  
Y. Huang ◽  
G. Yang
Keyword(s):  
Immune Response ◽  
Western Blot ◽  
Alveolar Macrophages ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Splenic Lymphocytes ◽  
Rt Pcr ◽  
Tnf Α ◽  
Pulmonary Alveolar Macrophages

Abstract Neuromedin S (NMS), a 36-amino acid neuropeptide, has been found to be involved in the regulation of the endocrine activity. It has been also detected in immune tissues in mammals, what suggests that NMS may play an important role in the regulation of immune response. The aim of this study was to demonstrate the presence of NMS receptor 1 (NMU1R) and effect of NMS in pig splenic lymphocytes (SPLs) and pulmonary alveolar macrophages (PAMs). The presence of NMU1R in pig SPLs and PAMs was respectively confirmed by reverse transcription-polymerase chain reaction (RT-PCR), western blot analysis and immunocytochemical methods. Furthermore, SPL proliferation was analyzed using the 3-(4,5)-dimethyl-thiahiazo-(-2-yl)-3,5-di-phenytetrazoliumromide (MTT) method. Additionally, the secretion of interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) in PAMs was all measured by enzyme-linked immunosorbent assay (ELISA) kits. In the present study, the results of RT-PCR and western blot analysis revealed that NMU1R mRNA and protein were both expressed in pig SPLs and PAMs, and the immunocytochemical investigations further revealed that the positive signal of NMU1R immunoreactivity was observed in plasma membranes of both SPLs and PAMs. In the in vitro study, we found that at concentrations of 0.001-1000 nM NMS alone or combined with lipopolysaccharide or phytohemagglutinin significantly increased SPL proliferation. Application of ELISA method showed that NMS could induce the secretion of the pro-inflammatory cytokines IL-1β, IL-6 and TNF-α in PAMs. These results suggest that NMS can act as a potently positive pro-inflammatory factor and immunomodulatory agent that affects the immune response of immune cells by combining with its receptor NMU1R.

FOXM1 regulates the proliferation, apoptosis and inflammatory response of keratinocytes through the NF-κB signaling pathway

2021 ◽  
pp. 096032712098422
Author(s):  
Mi Zhou ◽  
Jing Shi ◽  
Shaobo Lan ◽  
Xianjun Gong
Keyword(s):  
Cell Proliferation ◽  
Western Blot ◽  
Caspase 3 ◽  
Normal Skin ◽  
Psoriatic Skin ◽  
Hacat Cells ◽  
Expression Levels ◽  
Qrt Pcr ◽  
Tnf Α

Psoriasis is a common immune-mediated and genetic skin disease. Forkhead box M1 (FOXM1) is a member of FOX family that has been found to modulate skin disorders. However, its role in psoriasis remains unknown. Thus, we aimed to investigate the effect of FOXM1 on keratinocytes in response to tumor necrosis factor-α (TNF-α). The expression levels of FOXM1 in psoriasis tissues and normal skin tissues were examined using qRT-PCR and western blot. HaCaT cells were stimulated by TNF-α to mimic psoriasis in vitro. MTT assay was performed to assess cell proliferation. The caspase-3 activity and expression levels of bcl-2 and bax were determined to indicate cell apoptosis. The mRNA and secretion levels of IL-6, IL-23 and TGF-β were determined by qRT-PCR and ELISA, respectively. The NF-κB activation was assessed using western blot analysis. Our results demonstrated that FOXM1 was highly upregulated in psoriatic skin tissues and TNF-α-stimulated HaCaT cells. Knockdown of FOXM1 repressed cell proliferation of TNF-α-stimulated HaCaT cells. Knockdown of FOXM1 caused significant increases in caspase-3 activity, bax expression and decrease in bcl-2 expression in TNF-α-stimulated HaCaT cells. Moreover, FOXM1 knockdown also suppressed the TNF-α-induced production of IL-6, IL-23, and TGF-β in HaCaT cells. However, FOXM1 overexpression showed the opposite effect. Furthermore, the TNF-α-induced NF-κB activation was prevented by FOXM1 knockdown. Additionally, inhibition of NF-κB reversed the effects of FOXM1 on HaCaT cells. Taken together, these findings indicated that FOXM1 regulated cell proliferation, apoptosis and inflammation in TNF-α-induced HaCaT cells. The effects of FOXM1 were mediated by NF-κB pathway.

Sign in / Sign up

Export Citation Format

Share Document