Triggering of inflammatory response by myeloperoxidase-oxidized LDLAn oral presentation of the data was given before the Congress of the Beligian Society of Internal Medicine.

2006 ◽  
Vol 84 (5) ◽  
pp. 805-812 ◽  
Author(s):  
Karim Zouaoui Boudjeltia ◽  
Ilham Legssyer ◽  
Pierre Van Antwerpen ◽  
Roger Lema Kisoka ◽  
Sajida Babar ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Oxidized Ldl ◽  
Fold Increase ◽  
Ldl Oxidation ◽  
Early Event ◽  
Modified Ldl ◽  
Tnf Α ◽  
Cell Medium ◽  
Oxidation Theory ◽  
Cellular Types

The oxidation theory proposes that LDL oxidation is an early event in atherosclerosis and that oxidized LDL contributes to atherogenesis in triggering inflammation. In contrast to the copper-modified LDL, there are few studies using myeloperoxidase-modified LDL (Mox-LDL) as an inflammation inducer. Our aim is to test whether Mox-LDL could constitute a specific inducer of the inflammatory response. Albumin, which is the most abundant protein in plasma and which is present to an identical concentration of LDL in the intima, was used for comparison. The secretion of IL-8 by endothelial cells (Ea.hy926) and TNF-α by monocytes (THP-1) was measured in the cell medium after exposure of these cells to native LDL, native albumin, Mox-LDL, or Mox-albumin. We observed that Mox-LDL induced a 1.5- and 2-fold increase (ANOVA; P < 0.001) in IL-8 production at 100 µg/mL and 200 µg/mL, respectively. The incubation of THP-1 cells with Mox-LDL (100 µg/mL) increased the production of TNF-α 2-fold over the control. Native LDL, albumin, and Mox-albumin showed no effect in either cellular types. The myeloperoxidase-modified LDL increase in cytokine release by endothelial and monocyte cells and by firing both local and systemic inflammation could induce atherogenesis and its development.

Low-dose inhaled carbon monoxide attenuates the remote intestinal inflammatory response elicited by hindlimb ischemia-reperfusion

2009 ◽  
Vol 296 (1) ◽  
pp. G9-G14 ◽  
Author(s):  
Jeffrey R. Scott ◽  
Mark A. Cukiernik ◽  
Michael C. Ott ◽  
Aurelia Bihari ◽  
Amit Badhwar ◽  
...  
Keyword(s):  
Carbon Monoxide ◽  
Inflammatory Response ◽  
Proinflammatory Cytokine ◽  
Low Dose ◽  
Ischemia Reperfusion ◽  
Fold Increase ◽  
Leukocyte Recruitment ◽  
Leukocyte Rolling ◽  
Hindlimb Ischemia ◽  
Tnf Α

Heme oxygenase (HO) represents the rate-limiting enzyme in the degradation of heme into carbon monoxide (CO), iron, and biliverdin. Recent evidence suggests that several of the beneficial properties of HO, may be linked to CO. The objectives of this study were to determine if low-dose inhaled CO reduces remote intestinal leukocyte recruitment, proinflammatory cytokine expression, and oxidative stress elicited by hindlimb ischemia-reperfusion (I/R). Male mice underwent 1 h of hindlimb ischemia, followed by 3 h of reperfusion. Throughout reperfusion, mice were exposed to AIR or AIR + CO (250 ppm). Following reperfusion, the distal ileum was exteriorized to assess the intestinal inflammatory response by quantifying leukocyte rolling and adhesion in submucosal postcapillary venules with the use of intravital microscopy. Ileum samples were also analyzed for proinflammatory cytokine expression [tumor necrosis factor (TNF)-α and interleukin (IL)-1β] and malondialdehyde (MDA) with the use of enzyme-linked immunosorbent assay and thiobarbituric acid reactive substances assays, respectively. I/R + AIR led to a significant decrease in leukocyte rolling velocity and a sevenfold increase in leukocyte adhesion. This was also accompanied by a significant 1.3-fold increase in ileum MDA and 2.3-fold increase in TNF-α expression. Treatment with AIR + CO led to a significant reduction in leukocyte recruitment and TNF-α expression elicited by I/R; however, MDA levels remained unchanged. Our data suggest that low-dose inhaled CO selectively attenuates the remote intestinal inflammatory response elicited by hindlimb I/R, yet does not provide protection against intestinal lipid peroxidation. CO may represent a novel anti-inflammatory therapeutic treatment to target remote organs following acute trauma and/or I/R injury.

Curcumin ameliorates ethanol and nonethanol experimental pancreatitis

2003 ◽  
Vol 284 (1) ◽  
pp. G85-G95 ◽  
Author(s):  
Ilya Gukovsky ◽  
Christopher N. Reyes ◽  
Eva C. Vaquero ◽  
Anna S. Gukovskaya ◽  
Stephen J. Pandol
Keyword(s):  
Transcription Factor ◽  
Inflammatory Response ◽  
Neutrophil Infiltration ◽  
Experimental Pancreatitis ◽  
Early Event ◽  
Pancreatic Acini ◽  
Activation Of Transcription ◽  
Tnf Α ◽  
Severity Of The Disease ◽  
Oxide Synthase

Treatments for pancreatitis are limited. Activation of transcription factor NF-κB, a key regulator of inflammatory molecule expression, is an early event in experimental pancreatitis and correlates with the inflammatory response. We report here that curcumin, a natural phytochemical known to inhibit NF-κB and activator protein (AP)-1, another important proinflammatory transcription factor, ameliorates pancreatitis in two rat models. In both cerulein pancreatitis and pancreatitis induced by a combination of ethanol diet and low-dose CCK, curcumin improved the severity of the disease as measured by a number of parameters (histology, serum amylase, pancreatic trypsin, and neutrophil infiltration). Curcumin markedly inhibited NF-κB and AP-1 activation, assessed by DNA binding and degradation of inhibitory IκB proteins, and the induction of mRNAs for cytokines IL-6 and TNF-α, the chemokine KC, and inducible nitric oxide synthase in pancreas. Curcumin also blocked CCK-induced NF-κB and AP-1 activation in isolated pancreatic acini. Our findings indicate that blocking key signals of the inflammatory response ameliorates pancreatitis in both ethanol and nonethanol models. They suggest that curcumin, which is currently in clinical trials for cancer prevention, may be useful for treatment of pancreatitis.

Sorghum Fermented by Aspergillus oryzae NK Enhances Inhibition of Vascular Inflammation in TNF-α-stimulated Human Aortic Smooth Muscle Cells

2018 ◽  
Vol 88 (5-6) ◽  
pp. 309-318
Author(s):  
Hae Seong Song ◽  
Jung-Eun Kwon ◽  
Hyun Jin Baek ◽  
Chang Won Kim ◽  
Hyelin Jeon ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Inflammatory Response ◽  
Smooth Muscle Cells ◽  
Adhesion Molecule ◽  
Vascular Inflammation ◽  
Muscle Cells ◽  
Aortic Smooth Muscle Cells ◽  
Aortic Smooth Muscle ◽  
Tnf Α ◽  
Cox 2

Abstract. Sorghum bicolor L. Moench is widely grown all over the world for food and feed. The effects of sorghum extracts on general inflammation have been previously studied, but its anti-vascular inflammatory effects are unknown. Therefore, this study investigated the anti-vascular inflammation effects of sorghum extract (SBE) and fermented extract of sorghum (fSBE) on human aortic smooth muscle cells (HASMCs). After the cytotoxicity test of the sorghum extract, a series of experiments were conducted. The inhibition effects of SBE and fSBE on the inflammatory response and adhesion molecule expression were measured using treatment with tumor necrosis factor-α (TNF-α), a crucial promoter for the development of atherosclerotic lesions, on HASMCs. After TNF-α (10 ng/mL) treatment for 2 h, then SBE and fSBE (100 and 200 μg/mL) were applied for 12h. Western blotting analysis showed that the expression of vascular cell adhesion molecule-1 (VCAM-1) (2.4-fold) and cyclooxygenase-2 (COX-2) (6.7-fold) decreased, and heme oxygenase-1 (HO-1) (3.5-fold) increased compared to the TNF-α control when treated with 200 μg/mL fSBE (P<0.05). In addition, the fSBE significantly increased the expression of HO-1 and significantly decreased the expression of VCAM-1 and COX-2 compared to the TNF-α control in mRNA level (P<0.05). These reasons of results might be due to the increased concentrations of procyanidin B1 (about 6-fold) and C1 (about 30-fold) produced through fermentation with Aspergillus oryzae NK for 48 h, at 37 °C. Overall, the results demonstrated that fSBE enhanced the inhibition of the inflammatory response and adherent molecule expression in HASMCs.

A direct requirement of nuclear factor-κB for suppression of apoptosis in ventricular myocytes

2000 ◽  
Vol 279 (3) ◽  
pp. H939-H945 ◽  
Author(s):  
Shareef Mustapha ◽  
Alla Kirshner ◽  
Danielle De Moissac ◽  
Lorrie A. Kirshenbaum
Keyword(s):  
Dna Binding ◽  
Gene Transcription ◽  
Ventricular Myocytes ◽  
Vital Staining ◽  
Fold Increase ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Cytoplasmic Factor ◽  
Tnf Α ◽  
Factor Α

Nuclear factor-κB (NF-κB) is a ubiquitously expressed cellular factor regulated by the cytoplasmic factor inhibitor protein κBα (IκBα). Activation of NF-κB by cytokines, including tumor necrosis factor-α (TNF-α), requires the phosphorylation and degradation of IκBα. An anti-apoptotic role for NF-κB has recently been suggested. In the present study, we ascertained whether death-promoting signals and apoptosis mediated by TNF-α are suppressed by NF-κB in postnatal ventricular myocytes. Stimulation of myocytes with TNF-α resulted in a 12.1-fold increase ( P < 0.01) in NF-κB-dependent gene transcription and DNA binding compared with controls. This was accompanied by a corresponding increase in the NF-κB target protein A20 as determined by Western blot analysis. Vital staining revealed that TNF-α was not cytotoxic to myocytes and did not provoke apoptosis. Adenovirus-mediated delivery of a nonphosphorylatable form of IκBα to inactivate NF-κB prevented TNF-α-stimulated NF-κB-dependent gene transcription and nuclear NF-κB DNA binding. Importantly, myocytes stimulated with TNF-α and defective for NF-κB activation resulted in a 2.2-fold increase ( P < 0.001) in apoptosis. To our knowledge, the data provide the first indication that a functional NF-κB signaling pathway is crucial for suppressing death-promoting signals mediated by TNF-α in ventricular myocytes.

scholarly journals 4-(Phenylsulfanyl) Butan-2-One Attenuates the Inflammatory Response Induced by Amyloid-β Oligomers in Retinal Pigment Epithelium Cells

Marine Drugs ◽  
2020 ◽  
Vol 19 (1) ◽  
pp. 1
Author(s):  
Peeraporn Varinthra ◽  
Shun-Ping Huang ◽  
Supin Chompoopong ◽  
Zhi-Hong Wen ◽  
Ingrid Y. Liu
Keyword(s):  
Retinal Pigment Epithelium ◽  
Inflammatory Response ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Amyloid Β ◽  
Age Related Macular Degeneration ◽  
Epithelial Cell Line ◽  
Age Related ◽  
Tnf Α ◽  
Cox 2

Age-related macular degeneration (AMD) is a progressive eye disease that causes irreversible impairment of central vision, and effective treatment is not yet available. Extracellular accumulation of amyloid-beta (Aβ) in drusen that lie under the retinal pigment epithelium (RPE) has been reported as one of the early signs of AMD and was found in more than 60% of Alzheimer’s disease (AD) patients. Extracellular deposition of Aβ can induce the expression of inflammatory cytokines such as IL-1β, TNF-α, COX-2, and iNOS in RPE cells. Thus, finding a compound that can effectively reduce the inflammatory response may help the treatment of AMD. In this research, we investigated the anti-inflammatory effect of the coral-derived compound 4-(phenylsulfanyl) butan-2-one (4-PSB-2) on Aβ1-42 oligomer (oAβ1-42) added to the human adult retinal pigment epithelial cell line (ARPE-19). Our results demonstrated that 4-PSB-2 can decrease the elevated expressions of TNF-α, COX-2, and iNOS via NF-κB signaling in ARPE-19 cells treated with oAβ1-42 without causing any cytotoxicity or notable side effects. This study suggests that 4-PSB-2 is a promising drug candidate for attenuation of AMD.

scholarly journals AB0713 PERIODONTAL DISEASES AND ITS ASSOCIATION WITH ANKYLOSING SPONDYLITIS/SPA: A SYSTEMATIC REVIEW

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1652.1-1652
Author(s):  
A. Pandey ◽  
V. Ravindran ◽  
M. Pandey ◽  
R. Rajak ◽  
V. Pandey
Keyword(s):  
Systematic Review ◽  
Ankylosing Spondylitis ◽  
Connective Tissue ◽  
Inflammatory Response ◽  
Periodontal Disease ◽  
Close Association ◽  
Case Control ◽  
Clinical Attachment Loss ◽  
Tnf Α ◽  
Host Inflammatory Response

Background:A close association between periodontal disease and Ankylosing spondylitis (AS) has long been specualted. Both diseases are characterized by dysregulation of the host inflammatory response, leading to further destruction of soft and hard connective tissue with there being evidence of increased levels of TNF-α and various interleukins in both patients of AS and periodontitis.Objectives:The aim of this systematic review was to appraise the available literature exploring the relationship between AS and periodontal disease.Methods:We searched Medline & Embase databases (from their inception till October 2019) using appropriate combinations of following search items with limits ‘(English, Human)’; Ankylosing spondylitis, spondyloarthritis, spondyloarthropathies, spondyloarthritides, spinal disease, musculoskeletal disease, Rheumatic disease AND periodontitis, periodontal disease, periodontoses, parodontoses, chronic periodontitis, gum disease, gingivitis, oral health, dental health, plaque index, bleeding on probing, probing pocket depth, clinical attachment loss. This search was supplemented by the manual search of bibliographies of articles selected and conferences proceedings of EULAR. Only be reviews, observational study of cross-sectional, cohort or case control type on adult patients with AS were selected. Data was extracted from a predesigned proforma. A close association between periodontal disease and Ankylosing spondylitis (AS) has long been specualted. Both diseases are characterized by dysregulation of the host inflammatory response, leading to further destruction of soft and hard connective tissue with there being evidence of increased levels of TNF-α and various interleukins in both patients of AS and periodontitis.Results:A total number of 984 articles were identified and 12 were selcted for detailed appraisal (Figure 1, PRISMA flow chart). They were all case control studies. The prevalence of periodontitis ranged from 38% to 88% in patients with AS whereas in the control group from 26% to 71 % in controls. Out of 12 studies, two showed significant changes in Plaque Index (PI), two studies showed altered Pocket Probing Depth (PPD), three showed significant increased in Clinical Attachment Loss (CAL) and increased Bleeding On Probing (BOP) was seen in 2 studies. In 7 studies, periodontitis was seen in a significant number of patients with AS (P<0.05). All studies reported that the prevalence of periodontal disease in AS patients was higher as compared to non-AS patients.Conclusion:Our systematic review found an association between AS and periodontal disease. Patients with AS show higher prevalence of periodontitis and a poor oral hygiene as compared to healthy controls. At practice level, this systematic review underscores the need for a collaboration between dentists and rheumatologist.Disclosure of Interests:None declared

scholarly journals Comparing the protective effects of resveratrol, curcumin and sulforaphane against LPS/IFN-γ-mediated inflammation in doxorubicin-treated macrophages

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Haidy A. Saleh ◽  
Eman Ramdan ◽  
Mohey M. Elmazar ◽  
Hassan M. E. Azzazy ◽  
Anwar Abdelnaser
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Response ◽  
Raw 264.7 Cells ◽  
Inos Mrna ◽  
No Production ◽  
Raw 264.7 ◽  
Mrna Levels ◽  
Protective Effects ◽  
Tnf Α ◽  
Ifn Γ

AbstractDoxorubicin (DOX) chemotherapy is associated with the release of inflammatory cytokines from macrophages. This has been suggested to be, in part, due to DOX-mediated leakage of endotoxins from gut microflora, which activate Toll-like receptor 4 (TLR4) signaling in macrophages, causing severe inflammation. However, the direct function of DOX on macrophages is still unknown. In the present study, we tested the hypothesis that DOX alone is incapable of stimulating inflammatory response in macrophages. Then, we compared the anti-inflammatory effects of curcumin (CUR), resveratrol (RES) and sulforaphane (SFN) against lipopolysaccharide/interferon-gamma (LPS/IFN-γ)-mediated inflammation in the absence or presence of DOX. For this purpose, RAW 264.7 cells were stimulated with LPS/IFN-γ (10 ng/mL/10 U/mL) in the absence or presence of DOX (0.1 µM). Our results showed that DOX alone is incapable of stimulating an inflammatory response in RAW 264.7 macrophages. Furthermore, after 24 h of incubation with LPS/IFN-γ, a significant increase in tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and inducible nitric oxide synthase (iNOS) mRNA levels was observed. Similarly, nitric oxide (NO) production and TNF-α and IL-6 protein levels were significantly upregulated. Moreover, in LPS/IFN-γ-treated macrophages, the microRNAs (miRNAs) miR-146a, miR-155, and miR-21 were significantly overexpressed. Interestingly, upon testing CUR, RES, and SFN against LPS/IFN-γ-mediated inflammation, only SFN was able to significantly reverse the LPS/IFN-γ-mediated induction of iNOS, TNF-α and IL-6 and attenuate miR-146a and miR-155 levels. In conclusion, SFN, at the transcriptional and posttranscriptional levels, exhibits potent immunomodulatory action against LPS/IFN-γ-stimulated macrophages, which may indicate SFN as a potential treatment for DOX-associated inflammation.

scholarly journals Let-7a-5p regulates the inflammatory response in chronic rhinosinusitis with nasal polyps

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Jianwei Zhang ◽  
Lei Han ◽  
Feng Chen
Keyword(s):  
Inflammatory Response ◽  
Chronic Rhinosinusitis ◽  
Nasal Polyps ◽  
Mapk Pathway ◽  
Inhibitory Effect ◽  
Luciferase Reporter ◽  
Western Blot Assay ◽  
Protein Levels ◽  
Tnf Α

Abstract Background Let-7a-5p is demonstrated to be a tumor inhibitor in nasopharyngeal carcinoma. However, the role of let-7a-5p in chronic rhinosinusitis with nasal polyps (CRSwNP) has not been reported. This study is designed to determine the pattern of expression and role of let-7a-5p in CRSwNP. Methods The expression level of let-7a-5p, TNF-α, IL-1β, and IL-6 in CRSwNP tissues and cells were detected by RT-qPCR. Western blot assay was carried out to measure the protein expression of the Ras-MAPK pathway. Dual luciferase reporter assay and RNA pull-down assay were used to explore the relationship between let-7a-5p and IL-6. Results Let-7a-5p was significantly downregulated in CRSwNP tissues and cells. Moreover, the mRNA expression of TNF-α, IL-1β and IL-6 was increased in CRSwNP tissues, while let-7a-5p mimic inhibited the expression of TNF-α, IL-1β and IL-6. Besides that, let-7a-5p was negatively correlated with TNF-α, IL-1β and IL-6 in CRSwNP tissues. In our study, IL-6 was found to be a target gene of let-7a-5p. Additionally, let-7-5p mimic obviously reduced the protein levels of Ras, p-Raf1, p-MEK1 and p-ERK1/2, while IL-6 overexpression destroyed the inhibitory effect of let-7a-5p on the Ras-MAPK pathway in CRSwNP. Conclusion We demonstrated that let-7a-5p/IL-6 interaction regulated the inflammatory response through the Ras-MAPK pathway in CRSwNP.

scholarly journals Cangrelor ameliorates CLP-induced pulmonary injury in sepsis by inhibiting GPR17

2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Qiancheng Luo ◽  
Rui Liu ◽  
Kaili Qu ◽  
Guorong Liu ◽  
Min Hang ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Lavage Fluid ◽  
Surface Expression ◽  
Pulmonary Injury ◽  
Protective Mechanisms ◽  
Tnf Α ◽  
Anti Platelet Drug ◽  
G Protein Coupled ◽  
Very High ◽  
Masson Staining

Abstract Background Sepsis is a common complication of severe wound injury and infection, with a very high mortality rate. The P2Y12 receptor inhibitor, cangrelor, is an antagonist anti-platelet drug. Methods In our study, we investigated the protective mechanisms of cangrelor in CLP-induced pulmonary injury in sepsis, using C57BL/6 mouse models. Results TdT-mediated dUTP Nick-End Labeling (TUNEL) and Masson staining showed that apoptosis and fibrosis in lungs were alleviated by cangrelor treatment. Cangrelor significantly promoted surface expression of CD40L on platelets and inhibited CLP-induced neutrophils in Bronchoalveolar lavage fluid (BALF) (p < 0.001). We also found that cangrelor decreased the inflammatory response in the CLP mouse model and inhibited the expression of inflammatory cytokines, IL-1β (p  < 0.01), IL-6 (p < 0.05), and TNF-α (p < 0.001). Western blotting and RT-PCR showed that cangrelor inhibited the increased levels of G-protein-coupled receptor 17 (GPR17) induced by CLP (p < 0.001). Conclusion Our study indicated that cangrelor repressed the levels of GPR17, followed by a decrease in the inflammatory response and a rise of neutrophils in BALF, potentially reversing CLP-mediated pulmonary injury during sepsis.

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