IL-6 and TNF-α Induced Obesity-Related Inflammatory Response Through Transcriptional Regulation of miR-146b

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.

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

Marine Drugs ◽

10.3390/md19010001 ◽

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.

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

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.1564 ◽

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

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

Scientific Reports ◽

10.1038/s41598-020-80804-1 ◽

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.

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

Diagnostic Pathology ◽

10.1186/s13000-021-01089-0 ◽

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.

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

European Journal of Medical Research ◽

10.1186/s40001-021-00536-4 ◽

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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Glycyrrhizin Attenuates Carcinogenesis by Inhibiting the Inflammatory Response in a Murine Model of Colorectal Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms22052609 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2609

Author(s):

Guifeng Wang ◽

Keiichi Hiramoto ◽

Ning Ma ◽

Nobuji Yoshikawa ◽

Shiho Ohnishi ◽

...

Keyword(s):

Colorectal Cancer ◽

Dna Damage ◽

Stem Cell ◽

Inflammatory Response ◽

Murine Model ◽

Licorice Root ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Stem Cell Markers ◽

Tnf Α

Glycyrrhizin (GL), an important active ingredient of licorice root, which weakens the proinflammatory effects of high-mobility group box 1 (HMGB1) by blocking HMGB1 signaling. In this study, we investigated whether GL could suppress inflammation and carcinogenesis in an azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced murine model of colorectal cancer. ICR mice were divided into four groups (n = 5, each)—control group, GL group, colon cancer (CC) group, and GL-treated CC (CC + GL) group, and sacrificed after 20 weeks. Plasma levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α were measured using an enzyme-linked immunosorbent assay. The colonic tissue samples were immunohistochemically stained with DNA damage markers (8-nitroguanine and 8-oxo-7,8-dihydro-2′-deoxy-guanosine), inflammatory markers (COX-2 and HMGB1), and stem cell markers (YAP1 and SOX9). The average number of colonic tumors and the levels of IL-6 and TNF-α in the CC + GL group were significantly lower than those in the CC group. The levels of all inflammatory and cancer markers were significantly reduced in the CC + GL group. These results suggest that GL inhibits the inflammatory response by binding HMGB1, thereby inhibiting DNA damage and cancer stem cell proliferation and dedifferentiation. In conclusion, GL significantly attenuates the pathogenesis of AOM/DSS-induced colorectal cancer by inhibiting HMGB1-TLR4-NF-κB signaling.

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The Inflammatory Response Induced by Aspartic Proteases of Candida albicans Is Independent of Proteolytic Activity

Infection and Immunity ◽

10.1128/iai.00789-10 ◽

2010 ◽

Vol 78 (11) ◽

pp. 4754-4762 ◽

Cited By ~ 35

Author(s):

Donatella Pietrella ◽

Anna Rachini ◽

Neelam Pandey ◽

Lydia Schild ◽

Mihai Netea ◽

...

Keyword(s):

Candida Albicans ◽

Inflammatory Response ◽

Proteolytic Activity ◽

Necrosis Factor Alpha ◽

Pathogenic Yeast ◽

Aspartic Proteases ◽

Akt Activation ◽

Tnf Α ◽

Factor Alpha ◽

Pepstatin A

ABSTRACT The secretion of aspartic proteases (Saps) has long been recognized as a virulence-associated trait of the pathogenic yeast Candida albicans. In this study, we report that different recombinant Saps, including Sap1, Sap2, Sap3, and Sap6, have differing abilities to induce secretion of proinflammatory cytokines by human monocytes. In particular Sap1, Sap2, and Sap6 significantly induced interleukin-1β (IL-1β), tumor necrosis factor alpha (TNF-α), and IL-6 production. Sap3 was able to stimulate the secretion of IL-1β and TNF-α. All Saps tested were able to induce Ca2+ influx in monocytes. Treatment of these Saps with pepstatin A did not have any effect on cytokine secretion, indicating that their stimulatory potential was independent from their proteolytic activity. The capacity of Saps to induce inflammatory cytokine production was also independent from protease-activated receptor (PAR) activation and from the optimal pH for individual Sap activity. The interaction of Saps with monocytes induced Akt activation and phosphorylation of IκBα, which mediates translocation of NF-κB into the nucleus. Overall, these results suggest that individual Sap proteins can induce an inflammatory response and that this phenomenon is independent from the pH of a specific host niche and from Sap enzymatic activity. The inflammatory response is partially dependent on Sap denaturation and is triggered by the Akt/NF-κB activation pathway. Our data suggest a novel, activity-independent aspect of Saps during interactions of C. albicans with the host.

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Involvement of Gr-1dull+ Cells in the Production of TNF-α and IL-17 and Exacerbated Systemic Inflammatory Response Caused by Lipopolysaccharide

Inflammation ◽

10.1007/s10753-013-9729-5 ◽

2013 ◽

Vol 37 (1) ◽

pp. 186-195 ◽

Cited By ~ 2

Author(s):

Daiki Tanno ◽

Yukiko Akahori ◽

Masahiko Toyama ◽

Ko Sato ◽

Daisuke Kudo ◽

...

Keyword(s):

Inflammatory Response ◽

Systemic Inflammatory Response ◽

Tnf Α

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Carbohydrate response element binding protein (ChREBP) modulates the inflammatory response of mesangial cells in response to glucose

Bioscience Reports ◽

10.1042/bsr20180767 ◽

2018 ◽

Vol 38 (6) ◽

Author(s):

Yan Chen ◽

Yan-Jun Wang ◽

Ying Zhao ◽

Jin-Cheng Wang

Keyword(s):

Diabetes Mellitus ◽

Inflammatory Response ◽

Mesangial Cells ◽

Binding Protein ◽

The Body ◽

Mrna Levels ◽

Diabetic Mice ◽

Response Element ◽

Tnf Α ◽

Element Binding Protein

Diabetic nephropathy (DN) is one of the most devastating complications of diabetes mellitus. Carbohydrate response element binding protein (ChREBP) is a basic helix–loop–helix leucine zipper transcription factor that primarily mediates glucose homeostasis in the body. The present study investigated the role of ChREBP in the pathogenesis of DN. The expression of ChREBP was detected in patients with type 2 diabetes mellitus (T2DM), diabetic mice, and mesangial cells. ELISA was used to measure cytokine production in mesangial cells. Flow cytometry analysis was performed to detect the apoptosis of mesangial cells in the presence of high glucose. The expression levels of ChREBP and several cytokines (TNF-α, IL-1β, and IL-6) were up-regulated in T2DM patients. The mRNA and protein levels of ChREBP were also significantly elevated in the kidneys of diabetic mice. Moreover, glucose treatment promoted mRNA levels of TNF-α, IL-1β, and IL-6 in mesangial cells. Glucose stimulation induced significant apoptosis of SV40 MES 13 cells. In addition, transfection with ChREBP siRNA significantly inhibited ChREBP expression. Consequently, the inflammatory responses and apoptosis were inhibited in SV40 MES 13 cells. These results demonstrated that ChREBP could mediate the inflammatory response and apoptosis of mesangial cells, suggesting that ChREBP may be involved in the pathogenesis of DN.

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