scholarly journals Astragaloside IV attenuates IL-1β secretion by enhancing autophagy in H1N1 infection

2020 ◽  
Vol 367 (4) ◽  
Author(s):  
Jing Zhang ◽  
Wanju Zhang ◽  
Lehao Ren ◽  
Yanchao He ◽  
Zhoufang Mei ◽  
...  
Keyword(s):  
Interleukin 1 ◽  
Mrna Level ◽  
Inflammatory Factors ◽  
H1n1 Infection ◽  
Astragaloside Iv ◽  
Pharmacological Activities ◽  
Intrinsic Mechanism ◽  
A Cell ◽  
Excessive Secretion ◽  
Anti Inflammation

ABSTRACT Excessive secretion of inflammatory factors (cytokine storm) plays a significant role in H1N1-induced acute pneumonia, and autophagy acts as a cell-intrinsic mechanism to regulate inflammation. Astragaloside IV (AS-IV), originating from the astragalus root, possesses multiple pharmacological activities, such as anti-inflammation. However, the influences of AS-IV on H1N1-induced autophagy and inflammation have remained elusive. It has been reported that H1N1 infection leads to the accumulation of autophagosomes but obstructs autophagosomes incorporating into lysosomes, whereas the present study showed that AS-IV enhanced autophagy activation in H1N1 infection. Furthermore, we found that AS-IV promoted H1N1-triggered formation of autophagosomes and autolysosomes. Additionally, it was noted that AS-IV did not affect viral replication, mRNA level of interleukin-1 beta (IL-1β) and pro-IL-1β protein level, but significantly decreased secretion of IL-1β, and chloroquine (CQ, as an inhibitor of autophagy) increased secretion of IL-1β in H1N1 infection. In conclusion, AS-IV stimulates the formation of autophagosomes and the fusion of autophagosomes and lysosomes in H1N1 infection and may lead to decreased IL-1β secretion.

scholarly journals The Potential Role of IL1RAP on Tumor Microenvironment-Related Inflammatory Factors in Stomach Adenocarcinoma

2021 ◽  
Vol 20 ◽  
pp. 153303382199528
Author(s):  
Qing Lv ◽  
Qinghua Xia ◽  
Anshu Li ◽  
Zhiyong Wang
Keyword(s):  
Tumor Microenvironment ◽  
Interleukin 1 ◽  
Mrna Level ◽  
Inflammatory Factors ◽  
Stomach Carcinoma ◽  
Downstream Target ◽  
Volume Weight

This study was performed to investigate the role of interleukin-1 receptor accessory protein (IL1RAP) in stomach carcinoma in vitro and in vivo, determine whether IL1RAP knockdown could regulate the development of stomach carcinoma, and elucidate the relationship between IL1RAP knockdown and inflammation by tumor microenvironment-related inflammatory factors in stomach carcinoma. We first used TCGA and GEPIA systems to predict the potential function of IL1RAP. Second, western blot and RT-PCR were used to analyze the expression, or mRNA level, of IL1RAP at different tissue or cell lines. Third, the occurrence and development of stomach carcinoma in vitro and in vivo were observed by using IL1RAP knockdown lentivirus. Finally, the inflammation of stomach carcinoma in vitro and in vivo was observed. Results show that in GEPIA and TCGA systems, IL1RAP expression in STAD tumor tissue was higher than normal, and high expression of IL1RAP in STAD patients had a worse prognostic outcome. Besides, GSEA shown IL1RAP was negative correlation of apopopsis, TLR4 and NF-κB signaling pathway. We also predicted that IL1RAP may related to IL-1 s, IL-33, and IL-36 s in STAD. The IL1RAP expression and mRNA level in tumor, or MGC803, cells were increased. Furthermore, IL1RAP knockdown by lentivirus could inhibit stomach carcinoma development in vitro and in vivo through weakening tumor cell proliferation, migration, invasion, therefore reducing tumor volume, weight, and biomarker levels, and increasing apoptotic level. Finally, we found IL1RAP knockdown could increase inflammation of tumor microenvironment-related inflammatory factors of stomach carcinoma, in vitro and in vivo. Our study demonstrates that IL1RAP is possibly able to regulate inflammation and apoptosis in stomach carcinoma. Furthermore, TLR4, NF-κB, IL-1 s, IL-33, and IL-36 s maybe the downstream target factor of IL1RAP in inflammation. These results may provide a new strategy for stomach carcinoma development by regulating inflammation.

scholarly journals Experimental Study of Antiatherosclerosis Effects with Hederagenin in Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Su-Hong Lu ◽  
Jian-Hua Guan ◽  
Yan-Li Huang ◽  
Yu-Wei Pan ◽  
Wei Yang ◽  
...  
Keyword(s):  
Statistical Data ◽  
Inflammatory Factors ◽  
Lipid Deposition ◽  
Pathological Changes ◽  
Pharmacological Activities ◽  
Antiplatelet Aggregation ◽  
Vascular Walls ◽  
Lipid Metabolism Disorders ◽  
Antiatherosclerotic Effect ◽  
Anti Inflammation

The research tries to establish Wistar rat’s model of atherosclerosis for evaluating the antiatherosclerotic effect of hederagenin and exploring its antiatherosclerosis-related mechanisms. The statistical data have shown that hederagenin exhibits multiple pharmacological activities in the treatment of hyperlipidemia, antiplatelet aggregation, liver protection, and anti-inflammation, indicating that hederagenin may exert a protective effect on vascular walls by improving lipid metabolism disorders and lipid deposition. The results show that hederagenin can correct the imbalance of endothelial function by inhibiting the release of large amounts of iNOS and increasing eNOS contents and inhibits the IKKβ/NF-κB signaling pathway to reduce the release of IL-6, IFN-γ, TNF-α, and other inflammatory factors. The experimental results indicated that hederagenin can inhibit or ameliorate the pathological changes associated with AS, displaying an excellent preventive function against AS.

scholarly journals Gypenosides Attenuate Lipopolysaccharide-Induced Neuroinflammation and Memory Impairment in Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Bombi Lee ◽  
Insop Shim ◽  
Hyejung Lee
Keyword(s):  
Neurodegenerative Diseases ◽  
Memory Impairment ◽  
Day Treatment ◽  
Interleukin 1 ◽  
Mrna Level ◽  
Inflammatory Factors ◽  
Bdnf Mrna ◽  
Proinflammatory Mediators ◽  
Tlr4 Mrna ◽  
Anti Inflammatory

Neuroinflammation is deliberated a major factor in various neurodegenerative diseases. Gypenosides (GPS) have pharmacological properties with multiple beneficial effects including anti-inflammatory, antioxidative, and protective properties. In the present study, whether GPS could improve cognitive dysfunction and chronic inflammation caused by injecting lipopolysaccharide (LPS) in the hippocampus was investigated. Effects of GPS on inflammatory factors in the hippocampus and the downstream mechanisms of these effects were also examined. Induction of LPS into the lateral ventricle caused inflammatory reactions and memory impairment on the rats. Every day treatment of GPS (25, 50, and 100 mg/kg) for 21 consecutive days attenuated spatial recognition, discrimination, and memory deficits. GPS treatment significantly decreased proinflammatory mediators such as interleukin-6 (IL-6), interleukin-1β (IL-1β), and nuclear factor-kappaB (NF-κB) levels in the brain. Furthermore, GPS reduced LPS-induced elevated levels of inducible nitric oxide synthase (iNOS) and toll-like receptor 4 (TLR4) mRNA and inhibition of brain-derived neurotrophic factor (BDNF) mRNA level. Collectively, these results showed that GPS may improve cognitive function and provide a potential therapy for memory impairment caused by neuroinflammation. Based on these, GPS may be effective in inhibiting the progress of neurodegenerative diseases by improving memory functions due to its anti-inflammatory activities and appropriate modulation of NF-κB/iNOS/TLR4/BDNF.

scholarly journals Cross-talk between IRAK-4 and the NADPH oxidase1

2007 ◽  
Vol 403 (3) ◽  
pp. 451-461 ◽  
Author(s):  
Sandrine Pacquelet ◽  
Jennifer L. Johnson ◽  
Beverly A. Ellis ◽  
Agnieszka A. Brzezinska ◽  
William S. Lane ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Nadph Oxidase ◽  
P38 Mapk ◽  
Interleukin 1 ◽  
Mitogen Activated Protein Kinase ◽  
Free System ◽  
Mitogen Activated Protein ◽  
A Cell ◽  
Tlr4 Activation

Exposure of neutrophils to LPS (lipopolysaccharide) triggers their oxidative response. However, the relationship between the signalling downstream of TLR4 (Toll-like receptor 4) after LPS stimulation and the activation of the oxidase remains elusive. Phosphorylation of the cytosolic factor p47phox is essential for activation of the NADPH oxidase. In the present study, we examined the hypothesis that IRAK-4 (interleukin-1 receptor-associated kinase-4), the main regulatory kinase downstream of TLR4 activation, regulates the NADPH oxidase through phosphorylation of p47phox. We show that p47phox is a substrate for IRAK-4. Unlike PKC (protein kinase C), IRAK-4 phosphorylates p47phox not only at serine residues, but also at threonine residues. Target residues were identified by tandem MS, revealing a novel threonine-rich regulatory domain. We also show that p47phox is phosphorylated in granulocytes in response to LPS stimulation. LPS-dependent phosphorylation of p47phox was enhanced by the inhibition of p38 MAPK (mitogen-activated protein kinase), confirming that the kinase operates upstream of p38 MAPK. IRAK-4-phosphorylated p47phox activated the NADPH oxidase in a cell-free system, and IRAK-4 overexpression increased NADPH oxidase activity in response to LPS. We have shown that endogenous IRAK-4 interacts with p47phox and they co-localize at the plasma membrane after LPS stimulation, using immunoprecipitation assays and immunofluorescence microscopy respectively. IRAK-4 was activated in neutrophils in response to LPS stimulation. We found that Thr133, Ser288 and Thr356, targets for IRAK-4 phosphorylation in vitro, are also phosphorylated in endogenous p47phox after LPS stimulation. We conclude that IRAK-4 phosphorylates p47phox and regulates NADPH oxidase activation after LPS stimulation.

scholarly journals Curcumin nanomicelle versus curcumin improves lipid profile, stress oxidative factors and inflammatory markers in patients undergoing coronary elective angioplasty; A Randomized Clinical Trial

2019 ◽  
Author(s):  
Bijan Helli ◽  
Hadis Gerami ◽  
Maria Kavianpour ◽  
Habib Heybar ◽  
Seyed Kianoosh Hosseini ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Lipid Profile ◽  
Inflammatory Markers ◽  
Interleukin 1 ◽  
Stress Index ◽  
Inflammatory Factors ◽  
Control Group ◽  
Controlled Clinical Trial ◽  
Double Blind ◽  
Stress Oxidative

Abstract Background: Curcumin exhibited antioxidant and anti-inflammatory effects. The aim of this study, assess and compare curcumin and nano- curcumin effects on lipid profile, oxidative stress index and inflammatory factors of heart patients.Methods: This Randomized, Double-Blind, Placebo-Controlled Clinical Trial conducted on 90 patients undergoing coronary elective angioplasty. Patients were randomly divided into 3 groups. The first group received a 500 mg capsule of curcumin daily. The second group received an 80 mg capsule of nano- curcumin daily. The placebo group also received capsules similar to curcumin for 8 weeks. Lipid profile, stress oxidative factors and inflammatory markers measured in baseline and end of the investigation.Results: At the end of study, statistically significant changes was seen in the total cholesterol (TC), triglyceride (TG) and low density lipoprotein (LDL) in the intervention groups to the control group (p<0.05). These changes in the nano-curcumin group were greater than the curcumin group. Curcumin and nano-curcumin supplementation also caused a statistically significant improvement in plasma levels of total antioxidant capacity (TAC), malondialdehyde (MDA), Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), high-sensitivity C-reactive protein (hs-CRP), Interleukin 1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) in comparison to the placebo (p<0.05).Conclusion: Complementary therapy of cardiovascular patients with curcumin and nano-curcumin supplements, could improve lipid profile, stress oxidative index and, inflammatory factors. The effects of curcumin on nano formula may be better for cardiac patients due to high bioavailability. However, further investigation is suggested in this regard.

scholarly journals Toll9 from Bombyx mori functions as a pattern recognition receptor that shares features with Toll-like receptor 4 from mammals

2021 ◽  
Vol 118 (19) ◽  
pp. e2103021118
Author(s):  
Ruonan Zhang ◽  
Xiaofeng Li ◽  
Jie Zhang ◽  
Yanjun Li ◽  
Yuan Wang ◽  
...  
Keyword(s):  
Pattern Recognition ◽  
Bombyx Mori ◽  
Interleukin 1 ◽  
Structural Data ◽  
Pattern Recognition Receptor ◽  
Inflammatory Factors ◽  
Microbial Infection ◽  
Mammalian Tlrs ◽  
Tir Domains ◽  
Recognition Receptor

Toll/Toll-like receptors (TLRs) are key regulators of the innate immune system in both invertebrates and vertebrates. However, while mammalian TLRs directly recognize pathogen-associated molecular patterns, the insect Toll pathway is thought to be primarily activated by binding Spätzle cytokines that are processed from inactive precursors in response to microbial infection. Phylogenetic and structural data generated in this study supported earlier results showing that Toll9 members differ from other insect Tolls by clustering with the mammalian TLR4 group, which recognizes lipopolysaccharide (LPS) through interaction with myeloid differentiation-2 (MD-2)–like proteins. Functional experiments showed that BmToll9 from the silkmoth Bombyx mori also recognized LPS through interaction with two MD-2–like proteins, previously named BmEsr16 and BmPP, that we refer to in this study as BmMD-2A and BmMD-2B, respectively. A chimeric BmToll9–TLR4 receptor consisting of the BmToll9 ectodomain and mouse TLR4 transmembrane and Toll/interleukin-1 (TIR) domains also activated LPS-induced release of inflammatory factors in murine cells but only in the presence of BmMD-2A or BmMD-2B. Overall, our results indicate that BmToll9 is a pattern recognition receptor for LPS that shares conserved features with the mammalian TLR4–MD-2–LPS pathway.

scholarly journals Control of hemopoiesis by a bone marrow stromal cell clone: lipopolysaccharide- and interleukin-1-inducible production of colony- stimulating factors

Blood ◽  
1987 ◽  
Vol 69 (2) ◽  
pp. 682-691 ◽  
Author(s):  
D Rennick ◽  
G Yang ◽  
L Gemmell ◽  
F Lee
Keyword(s):  
Bone Marrow ◽  
Stromal Cell ◽  
Cell Clone ◽  
Interleukin 1 ◽  
Mrna Level ◽  
Adherent Cell ◽  
Mouse Bone Marrow ◽  
Activated T Cells ◽  
Gm Csf ◽  
Cell Layers

A stromal cell line, GY30, was cloned from mouse bone marrow adherent cell layers. In culture, GY30 cells sustain the production of granulocyte-macrophage progenitor cells (GM-CFU) but fail to support the survival of pluripotential stem cells (CFU-S). GY30 cells secrete two growth factor activities distinct from interleukin-3 (IL-3), IL-2, and macrophage colony-stimulating factor (M-CSF) but functionally similar to GM-CSF and G-CSF. The production of both CSFs is increased 70- to 200-fold by treating GY30 cells with lipopolysaccharide or IL-1. RNA blot analysis reveals the presence of GM-CSF and G-CSF transcripts and demonstrates that IL-1 regulates the production of both factors at the mRNA level. Further, these studies show that the GM-CSF secreted by GY30 cells is structurally similar to the GM-CSF produced by activated T cells.

scholarly journals Maladaptive oxidative stress cascade drives type I interferon hyperactivity in TNF activated macrophages promoting necrosis in murine tuberculosis granulomas

2020 ◽  
Author(s):  
Eric Brownhill ◽  
Shivraj M. Yabaji ◽  
Vadim Zhernovkov ◽  
Oleksii S. Rukhlenko ◽  
Kerstin Seidel ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Iron Chelator ◽  
Pathogen Transmission ◽  
Type I ◽  
Macrophage Response ◽  
Intrinsic Mechanism ◽  
A Cell ◽  
Novel Therapeutic Strategies ◽  
Jnk Activation ◽  
Inflammatory Milieu

ABSTRACTTuberculosis remains a critical infectious disease world-wide. The development of novel therapeutic strategies requires greater understanding of host factors that contribute to disease susceptibility. A major unknown in TB pathogenesis is the mechanism of necrosis in TB granulomas that leads to the massive lung tissue damage and cavity formation necessary for the pathogen transmission. In humans, TB progression has been linked to hyperactivity of type I IFN (IFN-I) pathway, the primary cause of which remains elusive.We studied the mechanistic drivers of pulmonary TB progression using a unique model B6J.C3-Sst1C3HeB/Fej Krmn mice that develop human-like necrotic TB granulomas and IFN-I hyperactivity. We established that IFNβ super-induction occurred in the susceptible macrophages in response to continuous TNF stimulation in the context of a dysregulated antioxidant defense. We observed that unresolving oxidative stress amplified the induction of IFNβ through JNK activation and induced the Integrated Stress Response via PKR activation as a compensatory pathway. Subsequently, PKR amplifies IFNβ upregulation, forming a positive feedback loop, maintaining the hyperinflammatory state in susceptible macrophages and leading to mitochondrial dysfunction. Thus, within the inflammatory milieu, a cell-intrinsic mechanism of chronic regulatory dysfunction and unresolved stress gradually weakens the macrophage and ultimately promotes the necrotization of TB granulomas. The aberrant macrophage response to TNF can be prevented by an iron chelator and inhibitor of lipid peroxidation, ferrostatin-1. Moreover, ferrostatin treatment increased macrophage survival and boosted bacterial control in the TNF-stimulated macrophages infected with virulent Mtb. These findings identify targets for host-directed therapeutics to interrupt necrotization in TB granulomas.

Evaluation of Serum Level of Interleukin 1 in Patients Suffering from Acute Coronary Syndrome, Admitted to the CCU Ward of AmirAlmomenin Hospital of Zahedan

2021 ◽  
Author(s):  
Hossein Ali Khazaei ◽  
Ahmad Bolouri ◽  
Hony Harati ◽  
Mehdi Mohammadi ◽  
Sayed Mohammad Nasiraldin Tabatabei ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Causes Of Death ◽  
Interleukin 1 ◽  
Developed Countries ◽  
Inflammatory Factors ◽  
Coronary Syndrome ◽  
Common Causes ◽  
Artery Disease ◽  
Flow Blockage ◽  
Q Wave

Background: Atherosclerosis is a disease in which the particles of fat builds up in the blood vessel’s walls. This build up leads to blood flow blockage or can cause the arteries to narrow, but until the stenosis of the vessel is not more than 70 percent, there won’t be any obvious symptoms. Symptoms are dependent on the location of the stenosis that can bring about diseases such as, Unstable Angina (UA), Myocardial Infarction with Q Wave (MIQW) and Non Q Wave (NMIQW). The most common causes of death in most developed countries is Coronary Artery Disease (CAD), and since the inflammatory factors are one of the causes of these diseases, we decided to evaluate the level of the Interleukin-1 (IL-1) in patients with acute coronary syndrome. Methods: 90 patients, suffering from the acute coronary syndrome were selected, which were previously diagnosed and referred to a cardiologist in the Imam Ali Ebneh hospital’s cardiac ward, in 2011. Five ml of periphery blood was obtained from each patient, after 24 hours of hospitalization. Using the ELISA method, the level of interleukin-1 was measured in the three groups of patients, each with symptoms of UA, MIQW and MINQW. Results: Our findings, showed the highest level of interleukin-1 in the MIQW patients, with the average of 46.55 pg/ml and, the lowest level in the MINQW patients, with the average of 28.17 pg/ml. Moreover, the average level of IL-1 in the patient’s serum with UA, is determined equal to 31.28 pg/ml. Although, there was no significant correlations between the type of MI development and UA, there was a significant correlation between the level of IL-1 and the type of MI development. Conclusion: Despite the fact, that the level of IL-1 was higher than normal in all the group types, and no significant correlation between the type of MI development and UA was found, there was statistically a significant correlation between the types of MI development and the level of IL-1.

Archidendron lucidum Exerts Anti-Inflammatory Effects by Targeting PDK1 in the NF-κB Pathway

2020 ◽  
Vol 48 (02) ◽  
pp. 429-444
Author(s):  
Minkyeong Jo ◽  
Young-Su Yi ◽  
Jae Youl Cho
Keyword(s):  
Signaling Pathway ◽  
Hplc Analysis ◽  
Inflammatory Diseases ◽  
Interleukin 1 ◽  
Inflammatory Activity ◽  
Raw264.7 Cells ◽  
Luciferase Reporter ◽  
No Production ◽  
Pharmacological Activities ◽  
Anti Inflammatory

Pharmacological activities of some Leguminosae family members were reported. Pharmacological activities of Archidendron lucidum, a Leguminosae family member have never been explored. Therefore, this study investigated anti-inflammatory effects of an Archidendron lucidum methanol extract (Al-ME). In this study, anti-inflammatory effects of Al-ME were investigated in LPS-stimulated RAW264.7 cells and HCl/EtOH-induced gastritis mice by MTT assay, nitric oxide (NO) production assay, semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), luciferase reporter assay, and Western blotting. High-performance liquid chromatography (HPLC) analysis identified ethnopharmacological compounds in Al-ME. Al-ME inhibited NO production without cytotoxicity in peritoneal macrophages and RAW264.7 cells stimulated with LPS or Pam3CSK4. Al-ME downregulated mRNA expression of inflammatory genes (inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2)) and pro-inflammatory cytokines (tumor necrosis factor-[Formula: see text] (TNF-[Formula: see text]), interleukin-1[Formula: see text] (IL-1[Formula: see text]), and IL-6). Al-ME exerted anti-inflammatory activity in LPS-stimulated RAW264.7 cells by inhibiting nuclear factor-kappa B (NF-[Formula: see text]B) signaling pathway. HPLC analysis identified quercetin, luteolin, and kaempferol as major anti-inflammatory components in Al-ME. Al-ME ameliorated HCl/EtOH-induced gastritis symptoms in mice by suppressing iNOS and IL-6 mRNA expressions and I[Formula: see text]B[Formula: see text] phosphorylation. Therefore, these results suggest that Al-ME exhibited anti-inflammatory activity by targeting NF-[Formula: see text]B signaling pathway, implying that Al-ME could be potent anti-inflammatory medications to prevent and treat inflammatory diseases.

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