Involvement of Rho-kinase/IκB-α/NF-κB activation in IL-1β-induced inflammatory response and oxidative stress in human chondrocytes

2021 ◽  
pp. 1-9
Author(s):  
Rukiye Nalan Tiftik ◽  
Meryem Temiz-Reşitoğlu ◽  
Demet Sinem Güden ◽  
Gülsen Bayrak ◽  
İsmail Ün ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Response ◽  
Nadph Oxidase ◽  
Rho Kinase ◽  
Human Chondrocytes ◽  
Rock Inhibitor ◽  
Pathway Activation ◽  
Tnf Α ◽  
Cox 2 ◽  
And Oxidative Stress

It has been clearly indicated that osteoarthritis (OA) is an inflammatory and degenerative disease that could be promoted by Rho-kinase (ROCK); however, little is known about the role of ROCK/inhibitor κB alpha (IκB-α)/nuclear factor-κB (NF-κB) p65 pathway activation in interleukin-1β (IL-1β) induced inflammatory response and oxidative stress in primary human chondrocytes. To test this hypothesis, we focused on determining ROCK-II, IκB-α, p-IκB-α, NF-κB p65, p-NF-κB p65, IL-6, tumor necrosis factor alpha (TNF-α), cyclooxygenase-2 (COX-2), p22phox, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subtype 4 (NOX4) protein expression, ROCK-II activity, NADPH oxidase levels, and total antioxidant capacity (TAC) in the presence and absence of ROCK-inhibitor fasudil. IL-1β (2 ng·mL–1, 24 h) increased the expression of ROCK-II, p-IκB-α, NF-κB p65, p-NF-κB p65, IL-6, TNF-α, COX-2, and p22phox proteins, and decreased the expression of IκB-α, and the NOX4 protein level did not alter. ROCK activity and NADPH oxidase levels were increased, whereas the TAC was decreased by IL-1β. Fasudil (10−5–10−7 M) reversed all these changes induced by IL-1β. These results demonstrate that ROCK/IκB-α/NF-κB p65 pathway activation contributes to the IL-1β-induced inflammatory response and oxidative stress, and thus, ROCK inhibition might be a beneficial treatment option for OA patients mainly based on its anti-inflammatory and antioxidant effects.

scholarly journals Targeting ROS/NF-κB sigaling pathway by the seedless black Vitis vinifera polyphenols in CCl4-intoxicated kidney, lung, brain, and spleen in rats

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Noha H. Habashy ◽  
Ahmad S. Kodous ◽  
Marwa M. Abu-Serie
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Vitis Vinifera ◽  
Rat Kidney ◽  
Environmental Pollutant ◽  
Enhancing Effect ◽  
Tnf Α ◽  
Cox 2 ◽  
Histopathological Studies ◽  
And Oxidative Stress

AbstractCarbon tetrachloride (CCl4) is an abundant environmental pollutant that can generate free radicals and induce oxidative stress in different human and animal organs like the kidney, lung, brain, and spleen, causing toxicity. The present study evaluated the alleviative mechanism of the isolated polyphenolic fraction from seedless (pulp and skin) black Vitis vinifera (VVPF) on systemic oxidative and necroinflammatory stress in CCl4-intoxicated rats. Here, we found that the administration of VVPF to CCl4-intoxicated rats for ten days was obviously ameliorated the CCl4-induced systemic elevation in ROS, NO and TBARS levels, as well as MPO activity. Also, it upregulated the cellular activities of the enzymatic (SOD, and GPx) and non-enzymatic (TAC and GSH) antioxidants. Furthermore, the gene expression of the ROS-related necroinflammatory mediators (NF-κB, iNOS, COX-2, and TNF-α) in the kidney, brain, and spleen, as well as IL-1β, and IL-8 in the lung were greatly restored. The histopathological studies confirmed these biochemical results and showed a noticeable enhancing effect in the architecture of the studied organs after VVPF intake. Thus, this study indicated that VVPF had an alleviative effect on CCl4-induced necroinflammation and oxidative stress in rat kidney, lung, brain, and spleen via controlling the ROS/NF-κB pathway.

scholarly journals Oregano Essential Oil Attenuates RAW264.7 Cells from Lipopolysaccharide-Induced Inflammatory Response through Regulating NADPH Oxidase Activation-Driven Oxidative Stress

Molecules ◽  
2018 ◽  
Vol 23 (8) ◽  
pp. 1857 ◽  
Author(s):  
Chuanshang Cheng ◽  
Yi Zou ◽  
Jian Peng
Keyword(s):  
Oxidative Stress ◽  
Protein Kinase ◽  
Essential Oil ◽  
Inflammatory Response ◽  
Nadph Oxidase ◽  
Raw264.7 Cells ◽  
Oregano Essential Oil ◽  
Tnf Α ◽  
Raw264.7 Cell ◽  
Inflammatory Effect

Oregano is an aromatic plant widely distributed throughout the Mediterranean area and in Asia. Recent studies have revealed that the anti-inflammatory effect of essential oil in this plant. However, the mechanisms underlying the therapeutic potential have not been well elucidated. This study determined whether oregano essential oil (OEO) exerts an anti-inflammatory effect on lipopolysaccharide (LPS)-treated murine macrophage cells (RAW264.7 cells) in vitro and elucidated the possible underlying molecular mechanisms. The results showed that OEO (2.5–10 μg/mL) inhibited the expression and secretion of interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) in RAW264.7 cells treated with LPS (1 μg/mL). Consistent with the pro-inflammatory gene expression, the OEO treatment efficiently reduced the LPS-induced activation of mitogen-activated protein kinase, protein kinase B, and nuclear factor κB in RAW264.7 cells. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibition in Nox2 protein-silenced cells attenuated the mRNA expression of IL-1β, IL-6, and TNF-α in the LPS-induced RAW264.7 cells. The OEO inhibited the LPS-induced elevation of NADPH oxidase and oxidative stress. This result suggests that LPS induces RAW264.7 cell inflammation through the NADPH oxidase-mediated production of reactive oxygen species (ROS). In conclusion, OEO protects against the LPS-induced RAW264.7 cell inflammatory response through the NADPH oxidase/ROS pathway.

scholarly journals Yacon (Smallanthus sonchifolius): Effect on Integrity of Intestinal Barrier, Inflammatory Response and Oxidative Stress in Animal Model of Colon Cancer (P06-052-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Neuza Costa ◽  
Thaisa Verediano ◽  
Mirelle Viana ◽  
Maria Vaz-Tostes
Keyword(s):  
Oxidative Stress ◽  
Colon Cancer ◽  
Inflammatory Response ◽  
Intestinal Permeability ◽  
Immunoglobulin A ◽  
Intestinal Barrier ◽  
Short Chain Fatty Acids ◽  
Local Immunity ◽  
Tnf Α ◽  
And Oxidative Stress

Abstract Objectives To investigate the prebiotic effect of yacon, source of fructooligosaccharides (FOS), on the integrity of the intestinal barrier, inflammatory response and oxidative stress in rats with induced colon cancer. Methods 44 adult Wistar rats were distributed into 4 groups: S (without colon cancer and yacon; n = 10); C (with colon cancer without yacon; n = 12); Y (without colon cancer with yacon; n = 10); and CY (with colon cancer and yacon; n = 12). Animals of groups S and C received AIN-93 M diet and animals of groups Y and CY received the same diet but added with yacon flour containing 28.95% FOS, to provide 5% FOS in the diet, for 16 weeks. From week 4 to 8, the animals of C and CY groups received an intraperitoneal dose of 25 mg/kg body weight of 1.2-dimethylhydrazine (DMH-Sigma®) once a week. In the last week, 24h-urine collection was performed for intestinal permeability analysis using lactulose and mannitol. Blood sample was collected for the analysis of IL-10 and IL-12 cytokines (Milliplex® Map, Luminex®) and total antioxidant capacity - TAC (Elabscience®). Large intestine was collected for intraluminal pH, short chain fatty acids - SCFA (HPLC) and immunoglobulin A – sIgA (Cloud-Clone®) analysis. Normal distributed data were analyzed by Two-way ANOVA, followed by Newman-Keuls (p < 0.05), using GraphPad Prism®, version 7. Results Cancer-induced animals showed higher TNF-α, SCFA (acetate, propionate and butirate), and lower TAC. Yacon reduced intraluminal pH and lactulose/mannitol ratio, increased propionic acid in the feces, but showed no effect on IL-10, IL-12, TNF-α, and IL-10/IL-12 ratio. The levels of sIgA were increased only in the group fed yacon without cancer (group Y). Mannitol and TAC were higher in CY group, showing a significant interaction of yacon and colon cancer. Conclusions Yacon reduced pH, intestinal permeability and the oxidative stress associated with colon cancer. The local immunity (sIgA) was raised, although no effect was observed on cytokines with yacon consumption. Yacon is a rich source of FOS wich improves the intestinal barrier and mucosal immunity, particularly in healthy animals. Funding Sources CNPq, FAPES.

scholarly journals Si Miao San Attenuates Inflammation and Oxidative Stress in Rats with CIA via the Modulation of the Nrf2/ARE/PTEN Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Pan Shen ◽  
Yao Huang ◽  
Xin Ba ◽  
Weiji Lin ◽  
Kai Qin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
High Dose ◽  
Collagen Induced Arthritis ◽  
Rat Serum ◽  
Oxidative Stress Parameters ◽  
Tnf Α ◽  
Cox 2 ◽  
Synovial Tissues ◽  
Stress Damage ◽  
And Oxidative Stress

Objective. Si Miao San (SMS) is a traditional Chinese formula used in China to treat rheumatic diseases. To date, its mechanism in rheumatoid arthritis (RA) treatment is uncertain. Our study aims to assess the antiarthritic effects of SMS in experimental arthritic rats. Materials and Methods. SMS (8.63, 4.31, and 2.16 g/kg/day) was orally administered after the first immunization from day 14 to day 53. The effects of SMS on rats with collagen-induced arthritis (CIA) were evaluated by arthritis score and histological assessment. The levels of cytokines and anti-CII antibodies in rat serum were measured by ELISAs. The expression of oxidative stress parameters was detected by biochemical assay kits. The levels of Nrf2, HO-1, NQO1, and PTEN were determined by western blotting. Results. Medium- and high-dose SMS treatment significantly decreased arthritis scores and alleviated ankle joint histopathology in the rats with CIA. It inhibited the production of IL-6, TNF-α, COX-2, and PGE2 in rat serum. SMS also suppressed the expression of anti-CII antibodies IgG1 and IgG2a. Moreover, SMS significantly suppressed the levels of MDA and MPO in the synovial tissues while increasing the levels of SOD and CAT in the rats with CIA. The levels of Nrf2, HO-1, NQO1, and PTEN were upregulated by SMS in rat synovial tissues. Conclusions. This study demonstrated that SMS effectively alleviated the disease progression of CIA by decreasing the levels of proinflammatory cytokines and reducing oxidative stress damage, as indicated by IL-6, TNF-α, COX-2, and PGE2 levels; inhibiting the overproduction of MDA and MPO; and enhancing antioxidant enzymes by upregulating the Nrf2/ARE/PTEN signalling pathway.

Egg-Derived Peptide IRW Inhibits TNF-α-Induced Inflammatory Response and Oxidative Stress in Endothelial Cells

2010 ◽  
Vol 58 (20) ◽  
pp. 10840-10846 ◽  
Author(s):  
Wuyang Huang ◽  
Subhadeep Chakrabarti ◽  
Kaustav Majumder ◽  
Yanyan Jiang ◽  
Sandra T. Davidge ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Inflammatory Response ◽  
Tnf Α ◽  
And Oxidative Stress

scholarly journals ONE-LUNG VENTILATION PATIENTS: CLINICAL CONTEXT OF ADMINISTRATION OF DIFFERENT DOSES OF DEXMEDETOMIDINE

2021 ◽  
Author(s):  
Hui Jiang ◽  
Yu Kang ◽  
Chunlin Ge ◽  
Zhengying Zhang ◽  
Yan Xie
Keyword(s):  
Oxidative Stress ◽  
Lung Function ◽  
Inflammatory Response ◽  
Oxygen Saturation ◽  
Lung Ventilation ◽  
Intrapulmonary Shunt ◽  
One Lung Ventilation ◽  
Tnf Α ◽  
And Oxidative Stress ◽  
Different Doses

Background: To investigate the effects of different doses of dexmedetomidine on inflammatory response, oxidative stress, cerebral tissue oxygen saturation (SctO2) and intrapulmonary shunt in patients undergoing one-lung ventilation (OLV). Methods: Sixty patients undergoing open pulmonary lobectomy in our hospital from January 2016 to December 2017 were enrolled and randomly divided into high-dose dexmedetomidine group (group D1, 1 μg/kg, n=20), low-dose dexmedetomidine group (group D2, 0.5 μg/kg, n=20) and control group (group C, n=20). Then, arterial blood and internal jugular venous blood were taken before anesthesia induction (T0) and at 15 min after two-lung ventilation (T1) and 5 min (T2) and 30 min (T3) after OLV for later use. Next, the changes in hemodynamic parameters [mean arterial pressure (MAP), heart rate (HR) and pulse oxygen saturation (SpO2)] of patients were observed in each group. Enzyme-linked immunosorbent assay (ELISA) was carried out to detect serum inflammatory factors such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) and oxidative stress indicators [superoxide dismutase (SOD) and malondialdehyde (MDA)]. The changes in SctO2, arterial partial pressure of oxygen (PaO2) and intrapulmonary shunt Qs/Qt were observed. Additionally, the changes in lung function indicators like lung dynamic compliance (Cdyn) and airway peak pressure (Ppeak) were determined. Results: There were no statistically significant differences in the MAP, HR and SpO2 among three groups at each observation time point (P>0.05). At T2 and T3, the levels of serum IL-6, TNF-α and IL-8 were obviously decreased in group D1 and D2 compared with those in group C (P<0.05), and the decreases in group D1 were overtly larger than those in group D2, and the decreases at T3 were markedly greater than those at T2 (P<0.05). In comparison with group C, group D1 and D2 had notably reduced levels of serum reactive oxygen species (ROS) and MDA (P<0.05) and remarkably increased SOD content (P<0.05) at T2 and T3, and the effects were markedly better in group D1 than those in group D2. Besides, they were significantly superior at T3 to those at T2 (P<0.05). The SctO2 in group D1 and D2 was evidently lowered at T2 and T3 compared with that at T0, and the decrease in group D1 was distinctly smaller than that in group D2 (P<0.05). The Qs/Qt was significantly lower in group D1 and D2 than that in group C at T2 and T3 (P<0.05), while the PaO2 content was notably raised (P<0.05), and the decrease and increase were significantly larger in group D1 than those in group D2, and they were obviously greater at T3 to those at T2 (P<0.05). At T0 and T1, no significant differences were detected in the Cdyn, Pplat and Ppeak among three groups. At T2 and T3, the Cdyn was significantly elevated, while the Pplat and Ppeak overtly declined (P<0.05), and group D1 had greater changes in comparison with group D2, and the changes were obviously more evident at T3 to those at T2 (P<0.05). Conclusions: Dexmedetomidine effectively ameliorates inflammatory response and oxidative stress, lowers oxygenation, Qs/Qt and the decrease in SctO2 and improves lung function during OLV, with good efficacy.

scholarly journals miRNA-221 Regulates Spinal Cord Injury-Induced Inflammatory Response through Targeting TNF-α Expression

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Feng Sun ◽  
Haiwei Zhang ◽  
Tianwen Huang ◽  
Jianhui Shi ◽  
Tianli Wei ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Inflammatory Response ◽  
Mouse Model ◽  
Luciferase Reporter ◽  
Spinal Cord Tissue ◽  
Tnf Α ◽  
Cord Injury ◽  
And Oxidative Stress

Objectives. To investigate the roles of miR-221 in spinal cord injury (SCI) as well as the underlying mechanism. Methods. A mouse model of SCI was generated and used to examine dynamic changes in grip strength of the mouse upper and lower limbs. The expression of miR-221 and tumor necrosis factor-α (TNF-α) was detected by RT-qPCR and Western blot. Levels of inflammation and oxidative stress in microglia cells of the injured mice overexpressing miR-221 were then measured by ELISA. Bioinformatics analysis and dual-luciferase reporter assay were conducted to identify the miR-221 target. Results. We successfully constructed SCI mouse model. The results of qRT-PCR showed that miR-221 was gradually upregulated in the spinal cord tissue of mice in the SCI group with the prolonged injury time. At the same time, the mRNA and protein of TNF-α gradually decreased. We further confirmed through cell experiments that the inflammatory factors TNF-α and IL-6, as well as iNOS and eROS, were upregulated in spinal cord microglia cells of SCI mice, and upregulation of miR-122 can inhibit their expression. Finally, the luciferase reporter experiment confirmed that miR-122 targeted TNF-α. Conclusions. We present evidence that miR-221 promotes functional recovery of the injured spinal cord through targeting TNF-α, while alleviating inflammatory response and oxidative stress.

scholarly journals Autocrine S100B in Astrocytes Promotes VEGF-dependent Inflammation and Oxidative Stress, and Causes Impairment of Neuroprotection

2021 ◽  
Author(s):  
xuebao wang ◽  
he yu ◽  
leping liu ◽  
baihui chen ◽  
shuya feng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hepatic Encephalopathy ◽  
Inflammatory Response ◽  
Underlying Mechanism ◽  
Minimal Hepatic Encephalopathy ◽  
Comprehensive Understanding ◽  
Vegf Expression ◽  
Cox 2 ◽  
The Impact ◽  
And Oxidative Stress

Abstract Background: Our previous study revealed that minimal hepatic encephalopathy (MHE) is strongly associated with neuroinflammation. Nevertheless, the underlying mechanism of the induction of inflammatory response in MHE astrocytes remains unclear. Methods: In this study, we further investigated the effect and mechanism of S100B, predominant isoform expressed and released from mature astrocytes, on MHE-like neuropathology in the MHE rat model. Results: We discovered that S100B expressions and autocrine were significantly increased in MHE rats and astrocytes isolated from MHE rats. Furthermore, we found that S100B stimulates VEGF expression via the interaction between TLR2 and RAGE in an autocrine manner. S100B-facilitated VEGF autocrine expression further led to a VEGFR2 and COX-2 interaction, which in turn induced the activation of NFƙB, eventually resulting in inflammation and oxidative stress caused by MHE astrocytes. Compared to WT astrocytes, impairment of MHE astrocytes supported neuronal growth in co-culture.Conclusions: To sum up, comprehensive-understanding of the impact of S100B-overexpressed MHE astrocyte on MHE pathology may provide insights into the etiology of MHE.

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