scholarly journals Vanillin Attenuates Pro-Inflammatory Factors in tMCAO Mice Model Via Inhibiting of TLR4/NF-kB Signal Pathway

2021 ◽  
Author(s):  
Lei Zhang ◽  
Ping Wang ◽  
Chunyi Li ◽  
Guolei Liao ◽  
Yihuan Huang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Motor Function ◽  
Inflammatory Cytokines ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Signal Pathway ◽  
Global Cerebral Ischemia ◽  
Tnf Α ◽  
Pro Inflammatory Cytokines

Abstract Purpose Vanillin has been reported to reduce hippocampal neuronal death in rats of global cerebral ischemia. However, the immunoregulatory mechanism of vanillin in ischemic mice is still unclear. Hence, this study aims to investigate the role of vanillin in transient middle cerebral artery occlusion (tMCAO) mice. Methods Transient cerebral ischemic stroke was induced by tMCAO surgery following by reperfusion in mice. After 24 hours of ischemia/reperfusion, Berderson scoring and TTC staining were used to evaluate neurological deficit and infarct volume, respectively. Furthermore, the expression of cytokines in ipsilateral hemisphere were detected by qPCR, ELISA and immunofluorescence. In vitro, LPS-stimulated primary and BV2 microglia cells were used to mimic neuroinflammation after ischemic stroke. Similarly, the expression of cytokines was detected by qPCR and ELISA. In addition, Western blotting was performed to evaluate the expression of Toll-like receptor 4 (TLR4), nuclear factor-κ-gene binding p65 (NF-κB p65) and phosphorylated NF-κB p65. Results Vanillin reduced infarct volume and improved motor function after ischemia/reperfusion. IL-1β and TNF-α were decreased in ischemic brain tissue of tMCAO mice after vanillin treatment. Similar changes were confirmed using the in vitro LPS-stimulated microglia cell model. Moreover, the decreasing expression of pro-inflammatory cytokines in vanillin group were related to TLR4/NF-κB signal pathway. Conclusions Taken together, vanillin decreased activation of microglia by inhibiting TLR4 /NF-κB signal pathway, and then reduced expression of pro-inflammatory cytokines IL-1β and TNF-α, which finally reduced infarct volume and improve motor function in tMCAO mice.

scholarly journals P0527AROLE OF PROMOTING INFLAMMATION OF KLF6 IN ACUTE KIDNEY INURY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Dan Li ◽  
Chenyu Li ◽  
Yan Xu
Keyword(s):  
Inflammatory Cytokines ◽  
Inflammatory Cytokine ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Tnf Α ◽  
Public Dataset ◽  
Anti Inflammatory ◽  
Anti Inflammatory Cytokine ◽  
Pro Inflammatory Cytokines

Abstract Background and Aims Acute kidney injury (AKI), commonly appeared in cardiac arrest, surgery and kidney transplantation which involved in ischemia-reperfusion (IR) injury of kidney. However, the mechanisms underlying inflammatory response in IR AKI is still unclear. Method Public dataset showed kruppel-like factor 6 (KLF6) was significantly highly expressed (P<0.05) in AKI, implies KLF6 might be associated with AKI. To evaluate the mechanism of KLF6 on IR AKI, 30 rats were randomly divided into sham and IR group, and were sacrificed at 0 h, 3 h, 6 h, 12 h or 24 h after IR. Results The results showed KLF6 expression was peaking at 6 h after IR, and the expression of pro-inflammatory cytokines MCP-1 and TNF-α were increased both in serum and kidney tissues after IR, while anti-inflammatory cytokine IL-10 was decreased after IR. Furthermore, in vitro results showed KLF6 knock-down reduced the pro-inflammatory cytokines expression and increased the anti-inflammatory cytokines expression. Conclusion These results suggest that (1) KLF6 might be a novel biomarker for early diagnosis of AKI and (2) targeting KLF6 expression may offer novel strategies to protect kidneys from IR AKI Figure KLF6, AKI, Control Inflammation

scholarly journals Senolytic Therapy for Cerebral Ischemia-Reperfusion Injury

2021 ◽  
Vol 22 (21) ◽  
pp. 11967
Author(s):  
Songhyun Lim ◽  
Tae Jung Kim ◽  
Young-Ju Kim ◽  
Cheesue Kim ◽  
Sang-Bae Ko ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Inflammatory Cytokines ◽  
Cellular Senescence ◽  
Therapeutic Potential ◽  
Ischemia Reperfusion ◽  
Severe Disabilities ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ir Injury

Ischemic stroke is one of the leading causes of death, and even timely treatment can result in severe disabilities. Reperfusion of the ischemic stroke region and restoration of the blood supply often lead to a series of cellular and biochemical consequences, including generation of reactive oxygen species (ROS), expression of inflammatory cytokines, inflammation, and cerebral cell damage, which is collectively called cerebral ischemia-reperfusion (IR) injury. Since ROS and inflammatory cytokines are involved in cerebral IR injury, injury could involve cellular senescence. Thus, we investigated whether senolytic therapy that eliminates senescent cells could be an effective treatment for cerebral IR injury. To determine whether IR induces neural cell senescence in vitro, astrocytes were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R). OGD/R induced astrocyte senescence and senescent cells in OGD/R-injured astrocytes were effectively eliminated in vitro by ABT263, a senolytic agent. IR in rats with intraluminal middle cerebral artery occlusion induced cellular senescence in the ischemic region. The senescent cells in IR-injured rats were effectively eliminated by intravenous injections of ABT263. Importantly, ABT263 treatment significantly reduced the infarct volume and improved neurological function in behavioral tests. This study demonstrated, for the first time, that senolytic therapy has therapeutic potential for cerebral IR injury.

scholarly journals Steroid Sulfates from Ophiuroids (Brittle Stars): Action on Some Factors of Innate and Adaptive Immunity

2016 ◽  
Vol 11 (6) ◽  
pp. 1934578X1601100
Author(s):  
Anna K Gazha ◽  
Lyudmila A. Ivanushko ◽  
Eleonora V. Levina ◽  
Sergey N. Fedorov ◽  
Tatyana S. Zaporozets ◽  
...  
Keyword(s):  
Adaptive Immunity ◽  
Inflammatory Cytokines ◽  
Brittle Stars ◽  
Innate And Adaptive Immunity ◽  
Functional Activities ◽  
In Vivo Experiments ◽  
Tnf Α ◽  
Pro Inflammatory Cytokines

The action of seven polyhydroxylated sterol mono- and disulfates (1-7), isolated from ophiuroids, on innate and adaptive immunity was examined in in vitro and in vivo experiments. At least, three of them (1, 2 and 4) increased the functional activities of neutrophils, including levels of oxygen-dependent metabolism, adhesive and phagocytic properties, and induced the expression of pro-inflammatory cytokines TNF-α and IL-8. Compound 4 was the most active for enhancing the production of antibody forming cells in the mouse spleen.

Crucial Factors of the Inflammatory Microenvironment (IL-1 beta/TNF-alpha/TIMP-1) Promote Maintenance of the Malignant Hemopoietic Clone of Myelofibrosis By Stimulating the in Vitro Survival/Proliferation/Migration of Circulating CD34+ stem/Progenitor Cells

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4094-4094
Author(s):  
Dorian Forte ◽  
Daria Sollazzo ◽  
Nicola Polverelli ◽  
Romano Marco ◽  
Lara Rossi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Inflammatory Cytokines ◽  
Stromal Cells ◽  
Colony Formation ◽  
Inflammatory Factors ◽  
Inflammatory Microenvironment ◽  
Cd34 Cells ◽  
Tnf Α ◽  
Pro Inflammatory Cytokines

Abstract Introduction. Myelofibrosis (MF), an acquired clonal disorder of the hematopoietic stem/progenitor cell (HSPC) with a dysregulation in JAK/STAT signalling (mutations in JAK2, MPL and Calreticulin (CALR) genes), is characterized by a state of chronic inflammation. It is argued that the up-regulated production of proinflammatory cytokines by both HSPCs and the surrounding stromal cells generates a microenvironment that selects for the malignant clone. Only recently, it has been hypothesized that the sustained inflammatory microenvironment of MF can alter crucial biological processes, leading to genomic instability and cancer progression. Here we tested the in vitro functional effects of pivotal players of the inflammatory microenvironment (the extracellular ATP nucleotide and selected cytokines, such as Interleukin (IL)-1β, Tumor Necrosis Factor (TNF)-α or the Tissue Inhibitor of Metalloproteinases-1 (TIMP-1)) on the HSPCs from MF patients. Methods: Circulating CD34+/CD34+ CD38- cells from MF patients (JAK2V617F (17 cases) and CALR (9 cases) mutations) or cord blood (CB; 8 samples) were phenotypically and functionally characterized after in vitro incubation with or without ATP (1000 μM), IL-1β (10 ng/mL), TNF-α (10 ng/mL) or TIMP-1 (100 ng/mL) (alone or in combination). Cells were then analyzed for survival/apoptosis (Annexin-V/Propidium Iodide staining), phenotype (evaluation of CD63 (TIMP-1 receptor), CXCR4 and CD38 expression), cell cycle and clonogenic capacity. Migration was assessed first towards a CXCL12 gradient in the presence or absence of the pro-inflammatory factors. In parallel experiments, CD34+ cells from MF patients were co-cultured with normal mesenchymal stromal cells (MSCs) in the presence or absence of the pro-inflammatory cytokines and then evaluated for their ability to migrate towards a CXCL12 gradient. Plasma TIMP-1, TNF-α, IL-1β and CXCL12 were measured by ELISA assay. Results: The plasma levels of TIMP-1, TNF-α, IL-1β, CXCL12 and the number of circulating CD34+, CD34+ CD38-, CD34+ CD63+, CD34+ CD184+ cells were increased in MF patients. According to mutational status, the CD34+ CD63+ cells were higher in the CALR+ patients. The survival of MF CD34+ cells was strongly stimulated by in vitro incubation with TNF-α or IL-1β as compared with the CB-derived CD34+ cells or untreated cells. By multiple cytokine combinations, IL-1β/TIMP-1, IL-1β /ATP or IL-1β /TNF-α treatments significantly promote the survival of MF CD34+ cells as compared with the normal counterparts or the untreated cells. Various combinations with IL-1β were also effective in stimulating survival of CD34+CD38- cells. IL-1β/TIMP-1 and IL-1β/TNF-α/TIMP-1, but not factors alone, significantly increased the CFU-C growth of MF patients as compared with the CB-derived counterparts and the untreated cells. Moreover, comparing CALR+ vs JAK2V617F+ patients, the colony formation of JAK2V617F+ patients was mainly promoted by the IL-1β/TNF-α treatment. Along with clonogenic capacity stimulation, exposure of CD34+ cells from MF patients to IL-1β/TNF-α/TIMP-1 significantly increases the S-phase cells, suggesting that these pro-inflammatory factors stimulated cell-cycle progression in dormant CD34+ MF cells. Migration of CD34+ cells from MF was significantly increased in CXCL12 treated cells. In addition, exposure of MF CD34+ cells to IL-1β/TNF-α, IL-1β/TIMP-1 or IL-1β/TNF-α/TIMP-1 significantly promotes cell migration in comparison with the CB-derived counterparts or SDF-1 alone. MF migrated cells in the presence of IL-1β/TNF-α significantly upregulate CD63 expression. Intriguingly, colony formation of MF migrated CD34+ cells in the presence of IL-1β/TNF-α or IL-1β/TNF-α/TIMP-1 was potently increased. Finally, co-culture systems with normal MSCs in the presence of pro-inflammatory factors revealed that MF CD34+ cells display increased migration ability toward CXCL12 gradient. Conclusions: Altogether our findings suggest that in MF the inflammatory niche plays a key role in the maintenance of the malignant clone. Thus, the interplay between the pro-inflammatory cytokines promote and select the HSPCs with higher proliferative activity, clonogenic potential and migration capability. Targeting these microenvironmental interactions may be a clinically relevant approach. D.F. and D.S. equally contributed Disclosures Martinelli: Pfizer: Consultancy; Ariad: Consultancy; Novartis: Consultancy, Speakers Bureau; MSD: Consultancy; AMGEN: Consultancy; BMS: Consultancy, Speakers Bureau; ROCHE: Consultancy.

scholarly journals Dectin-1/Syk signaling triggers neuroinflammation after ischemic stroke in mice

2019 ◽  
Author(s):  
Xin-chun Ye ◽  
Qi Hao ◽  
Wei-jing Ma ◽  
Qiu-chen Zhao ◽  
Wei-wei Wang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Brain Injury ◽  
Infarct Volume ◽  
Inos Expression ◽  
Microglial Cells ◽  
Brain Infarct ◽  
Tnf Α ◽  
Bv2 Microglial Cells ◽  
The Brain

Abstract Dendritic cell-associated C-type lectin-1 (Dectin-1) receptor has been reported to be involved in neuroinflammation in Alzheimer's disease and traumatic brain injury. The present study was designed to investigate the role of Dectin-1 and its downstream target spleen tyrosine kinase (Syk) in early brain injury after ischemic stroke using a focal cortex ischemic stroke model. Adult male C57BL/6J mice were subjected to a cerebral focal ischemia model of ischemic stroke. The neurological score, adhesive removal test and foot-fault test were evaluated on days 1, 3, 5 and 7 after ischemic stroke. Dectin-1, Syk, phosphorylated (p)-Syk, tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS) expression was analyzed via western blotting in ischemic brain tissue after ischemic stroke and in BV2 microglial cells subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) injury in vitro. The brain infarct volume and Iba1-positive cells were evaluated using Nissl’s and immunofluorescence staining, respectively. The Dectin-1 antagonist laminarin (LAM) and a selective inhibitor of Syk phosphorylation (piceatannol; PIC) were used for the intervention. Dectin-1, Syk, and p-Syk expression was significantly enhanced on days 3, 5 and 7 and peaked on day 3 after ischemic stroke. The Dectin-1 antagonist LAM or Syk inhibitor PIC decreased the number of Iba1-positive cells and TNF-α and iNOS expression, decreased the brain infarct volume and improved neurological functions on day 3 after ischemic stroke. In addition, the in vitro data revealed that Dectin-1, Syk and p-Syk expression was increased following the 3-h OGD and 0, 3 and 6 h of reperfusion in BV2 microglial cells. LAM and PIC also decreased TNF-α and iNOS expression 3 h after OGD/R induction. Dectin-1/Syk signaling plays a crucial role in inflammatory activation after ischemic stroke, and further investigation of Dectin-1/Syk signaling in stroke is warranted.

scholarly journals IKK-2 inhibitor TPCA-1 represses nasal epithelial inflammation in vitro

2011 ◽  
Vol 49 (2) ◽  
pp. 168-173
Author(s):  
F. Sachse ◽  
K. Becker ◽  
T.J. Basel ◽  
D. Weiss ◽  
C. Rudack
Keyword(s):  
Inflammatory Cytokines ◽  
Inflammatory Disease ◽  
Inflammatory Process ◽  
Nasal Polyposis ◽  
Paraffin Sections ◽  
Tnf Α ◽  
Epithelial Inflammation ◽  
Pro Inflammatory Cytokines

BACKGROUND: Nasal polyposis (NP) is considered a subgroup within chronic rhinosinusitis. NP can be further subdivided into aspirin sensitive- and aspirin tolerant types (ASNP/ ATNP). Although the true etiology of NP has not been identified so far, it is agreed that NP represents an inflammatory disease of the nasal mucosa. Alterations of cellular kinase activities including that of IKK-2 might play a role in this inflammatory process. METHODS: Paraffin sections of ASNP, ATNP and controls were immunostained with Phospho-IkB-α antibody that detects the direct IKK-2 product (IkB-α. Intensity of epithelial staining was analysed semi-quantitatively by two independent observers. In cultured nasal polyp epithelial cells (NPECs) epithelial derived cytokines IL-8 and GRO α were induced by TNF-α or Staphylococcal supernatants and subsequently repressed by IKK-2 inhibitor TPCA-1. RESULTS: Significant Phospho-IkB-α staining was observed in the nasal epithelium of ASNP compared to ATNP and controls suggesting strong IKK-2 activation in patients with ASNP in vivo. In vitro, pro-inflammatory cytokines IL-8 and GRO-α in NPECs were significantly repressed by TPCA-1. CONCLUSION: IKK-2 activity is increased in the subgroup of ASNP. IL-8 and GRO-α responses were repressed by IKK-2 inhibitor TPCA-1 in vitro. IKK-2 inhibitors might represent a potential target for anti-inflammatory intervention in ASNP.

scholarly journals MiR-200a-3p Accelerated Hypoxia/Reoxygenation Injury in HCM Cells by Enhancing IGF2R via Wnt/β-catenin Signalling Pathway

2021 ◽  
Vol 21 (02) ◽  
Author(s):  
Yaolei Ge
Keyword(s):  
Cell Viability ◽  
Inflammatory Cytokines ◽  
Caspase 3 ◽  
Signalling Pathway ◽  
Dependent Manner ◽  
Tnf Α ◽  
Reoxygenation Injury ◽  
Pro Inflammatory Cytokines ◽  
Hypoxia Reoxygenation

ABSTRACT The present study examined functions of miR-200a-3p accelerated progressions of HCM cells via IGF2R and Wnt/β-catenin signalling pathway after hypoxia/reoxygenation treatment in vitro. CCK-8 showed that cell viability of HCM was inhibited while apoptosis rates detected by flow cytometry were promoted in a time dependent manner after H/R (12 hours and 24 hours). Beyond that, Bcl-2 and c-IAP1 were decreased but Bax and caspase-3 were upregulated by H/R treatment. IL-1β, IL-6, TNF-α and NLRP3 were also increased after treatment. RT-qPCR showed increased expressions of miR-200a-3p by H/R treatment while its inhibitor elevated cell viability but depressed apoptosis rate and pro-inflammatory cytokines’ expressions. IGF2R was upregulated after H/R treatment and its downregulation magnified effects of suppressed miR-200a-3p. HIF-1α/Wnt/β -catenin signalling pathway was activated by miR-200a-3p and IGF2R while IWP-2 treatment abolished the activation of Wnt3a andβ -catenin, causing decreased apoptosis and pro-inflammatory cytokines’ expressions but accelerated the cell viability.

scholarly journals Maternal Serum Levels of Interferon-gamma, Tumor Necrotic Factor-alpha and Progesterone of Infertile Women on In vitro Fertilization before and after Treatment

2020 ◽  
pp. 38-44
Author(s):  
N. Osakue ◽  
C. C. Onyenekwe ◽  
F. A. Ehiaghe ◽  
J. E. Ahaneku ◽  
J. I. Ikechebelu ◽  
...  
Keyword(s):  
In Vitro Fertilization ◽  
Inflammatory Cytokines ◽  
First Trimester ◽  
Vitro Fertilization ◽  
Tnf Α ◽  
Before And After ◽  
First Trimester Of Pregnancy ◽  
Ifn Γ ◽  
Pro Inflammatory Cytokines

Background: In vitro fertilization (IVF) is an assisted reproductive technology (ART) that is widely used globally in the treatment of infertility. Infertility can occur due to male factors, female factors or both. Aim: This is the first Nigerian study that sets out to observe the levels and relationship between circulating pro-inflammatory cytokines (IFN-γ, TNF-α) and progesterone (PG) in Nigerian women undergoing in vitro fertilization pre and post treatment and their possible effect on pregnancy outcome. Materials and Methods: This observational study randomly selected sixty-two (62) infertile females below 45 year of age who enrolled in the IVF treatment at Lily Hospitals, Warri and Shepherd Specialist Hospital, Warri, Southern Nigeria. Only data of the thirteen (13) infertile females who became pregnant after the IVF treatment where followed up and presented in this study. Five (5) ml of whole blood were collected into plain tubes on day 3 of the menstrual cycle of all the participants from the ante-cubital vein before and after IVF procedure using standard laboratory collection technique. Ovarian stimulation was done using the long gonadotropin-releasing hormone agonist protocol. Oocyte retrieval transfer was done using ultrasound-guided fine-needle aspiration and embryo transfer was done using ultrasound-guided embryo transfer. IFN-γ, TNF-α and PG were estimated using enzyme-linked immunosorbent assay method. Results and Conclusion: Significant increase in the levels of TNF-α and PG at the second trimester and third trimester of pregnancy when compared with the first trimester of pregnancy (p = 0.000). While the level of IFN-γ was significantly increased in the second trimester of pregnancy when compared with the first trimester of pregnancy (p = 0.000). It is evident from the study that both pro-inflammatory cytokines (IFN-γ and TNF-α) act in synergy to maintain the level of progesterone which act as an anti-inflammatory agent to regulate the activities of the pro-inflammatory cytokines for successful oocytes implantation and maturation.

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