scholarly journals Anti-Inflammatory Effects of Metabolites from Antarctic Fungal Strain Pleosporales sp. SF-7343 in HaCaT Human Keratinocytes

2021 ◽  
Vol 22 (18) ◽  
pp. 9674
Author(s):  
Linsha Dong ◽  
Hye Jin Kim ◽  
Thao Quyen Cao ◽  
Zhiming Liu ◽  
Hwan Lee ◽  
...  
Keyword(s):  
Nuclear Translocation ◽  
Protoporphyrin Ix ◽  
Human Keratinocytes ◽  
Fungal Strain ◽  
Intercellular Adhesion Molecule ◽  
Mechanism Study ◽  
Intercellular Adhesion Molecule 1 ◽  
Barrier Dysfunction ◽  
Study Results ◽  
Anti Inflammatory

Chemical investigation of the Antarctic fungi Pleosporales sp. SF-7343 revealed four known secondary fungal metabolites: alternate C (1), altenusin (2), alternariol (3), and altenuene (4). The compound structures were identified primarily by NMR and MS analyses. Atopic dermatitis, an inflammatory disease, is driven by the abnormal activation of T helper (Th) 2 cells and barrier dysfunction. We attempted to identify the anti-inflammatory components of SF-7343. Initial screening showed that compounds 1 and 3 inhibited the secretion of interleukin-8 and -6 in tumor necrosis factor-α/interferon-γ-treated HaCaT cells, and these compounds also showed inhibitory effects on CCL5 and CCL22. Compounds 1 and 3 also downregulated the protein expression levels of intercellular adhesion molecule-1 and upregulated the expression of filaggrin and involcurin. The mechanism study results showed that compounds 1 and 3 inhibited nuclear translocation of nuclear factor-kappa B p65 and the phosphorylation of STAT1 and STAT3. Compound 1, but not compound 3, significantly promoted the expression of heme oxygenase (HO)-1. The effects of compound 1 were partly reversed by co-treatment with a HO-1 inhibitor, tin protoporphyrin IX. Taken together, this study demonstrates the potential value of Antarctic fungal strain SF-7343 isolates as a bioresource for bioactive compounds to prevent skin inflammation.

scholarly journals Asef mediates HGF protective effects against LPS-induced lung injury and endothelial barrier dysfunction

2015 ◽  
Vol 308 (5) ◽  
pp. L452-L463 ◽  
Author(s):  
Fanyong Meng ◽  
Angelo Meliton ◽  
Nurgul Moldobaeva ◽  
Gokhan Mutlu ◽  
Yoshihiro Kawasaki ◽  
...  
Keyword(s):  
Lung Injury ◽  
Adhesion Molecule ◽  
Endothelial Barrier ◽  
Intercellular Adhesion Molecule ◽  
Protective Effects ◽  
Nucleotide Exchange ◽  
Intercellular Adhesion Molecule 1 ◽  
Barrier Dysfunction ◽  
Gram Negative ◽  
Anti Inflammatory

Increased vascular endothelial permeability and inflammation are major pathological mechanisms of pulmonary edema and its life-threatening complication, the acute respiratory distress syndrome (ARDS). We have previously described potent protective effects of hepatocyte growth factor (HGF) against thrombin-induced hyperpermeability and identified the Rac pathway as a key mechanism of HGF-mediated endothelial barrier protection. However, anti-inflammatory effects of HGF are less understood. This study examined effects of HGF on the pulmonary endothelial cell (EC) inflammatory activation and barrier dysfunction caused by the gram-negative bacterial pathogen lipopolysaccharide (LPS). We tested involvement of the novel Rac-specific guanine nucleotide exchange factor Asef in the HGF anti-inflammatory effects. HGF protected the pulmonary EC monolayer against LPS-induced hyperpermeability, disruption of monolayer integrity, activation of NF-kB signaling, expression of adhesion molecules intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, and production of IL-8. These effects were critically dependent on Asef. Small-interfering RNA-induced downregulation of Asef attenuated HGF protective effects against LPS-induced EC barrier failure. Protective effects of HGF against LPS-induced lung inflammation and vascular leak were also diminished in Asef knockout mice. Taken together, these results demonstrate potent anti-inflammatory effects by HGF and delineate a key role of Asef in the mediation of the HGF barrier protective and anti-inflammatory effects. Modulation of Asef activity may have important implications in therapeutic strategies aimed at the treatment of sepsis and acute lung injury/ARDS-induced gram-negative bacterial pathogens.

scholarly journals Anti-Inflammatory Effects of Compounds from Cudrania tricuspidata in HaCaT Human Keratinocytes

2021 ◽  
Vol 22 (14) ◽  
pp. 7472
Author(s):  
Wonmin Ko ◽  
Nayeon Kim ◽  
Hwan Lee ◽  
Eun-Rhan Woo ◽  
Youn-Chul Kim ◽  
...  
Keyword(s):  
Human Keratinocytes ◽  
Interferon Γ ◽  
Intercellular Adhesion Molecule ◽  
Cytotoxic Activities ◽  
Root Bark ◽  
Intercellular Adhesion Molecule 1 ◽  
Cudrania Tricuspidata ◽  
Expression Levels ◽  
Anti Inflammatory ◽  
L 14

The root bark of Cudrania tricuspidata has been reported to have anti-sclerotic, anti-inflammatory, antioxidant, neuroprotective, hepatoprotective, and cytotoxic activities. In the present study, the effect of 16 compounds from C. tricuspidata on tumor necrosis factor-α+interferon-γ-treated HaCaT cells were investigated. Among these 16 compounds, 11 decreased IL-6 production and 15 decreased IL-8 production. The six most effective compounds, namely, steppogenin (2), cudraflavone C (6), macluraxanthone B (12), 1,6,7-trihydroxy-2-(1,1-dimethyl-2-propenyl)-3- methoxyxanthone (13), cudraflavanone B (4), and cudratricusxanthone L (14), were selected for further experiments. These six compounds decreased the expression levels of chemokines, such as regulated on activation, normal T cell expressed and secreted (RANTES) and thymus and activation-regulated chemokine (TARC), and downregulated the protein expression levels of intercellular adhesion molecule-1. Compounds 2, 6, 12, 4, and 14 inhibited nuclear factor-kappa B p65 translocation to the nucleus; however, compound 13 showed no significant effects. In addition, extracellular signal regulatory kinase-1/2 phosphorylation was only inhibited by compound 14, whereas p38 phosphorylation was inhibited by compounds 13 and 4. Taken together, the compounds from C. tricuspidata showed potential to be further developed as therapeutic agents to suppress inflammation in skin cells.

scholarly journals Silibinin Inhibits ICAM-1 Expression via Regulation of N-Linked and O-Linked Glycosylation in ARPE-19 Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-13
Author(s):  
Yi-Hao Chen ◽  
Ching-Long Chen ◽  
Chang-Min Liang ◽  
Jy-Been Liang ◽  
Ming-Cheng Tai ◽  
...  
Keyword(s):  
Nuclear Translocation ◽  
Transmembrane Protein ◽  
Reporter Gene Assay ◽  
Intercellular Adhesion Molecule ◽  
Inhibitory Effects ◽  
Intercellular Adhesion Molecule 1 ◽  
Reporter Activity ◽  
Gene Assay ◽  
Stat1 Signaling ◽  
Necrosis Factor

To evaluate the effects of silibinin on intercellular adhesion molecule-1 (ICAM-1) expression, we used ARPE-19 cells as a model in which tumor necrosis factor (TNF-α) and interferon (IFN-γ) enhanced ICAM-1 expression. This upregulation was inhibited by silibinin. In an adherence assay using ARPE-19 and THP-1 cells, silibinin inhibited the cell adhesion function of ICAM-1. The inhibitory effects of silibinin on ICAM-1 expression were mediated via the blockage of nuclear translocation of p65 proteins in TNF-αand phosphorylation of STAT1 in IFN-γ-stimulated cells. In addition, silibinin altered the degree of N-linked glycosylation posttranslationally in ARPE-19 cells by significantly enhancingMGAT3gene expression. Silibinin can increase the O-GlcNAc levels of glycoproteins in ARPE-19 cells. In a reporter gene assay, PUGNAc, which can also increase O-GlcNAc levels, inhibited NF-κB reporter activity in TNF-α-induced ARPE-19 cells and this process was augmented by silibinin treatment. Overexpression ofOGTgene was associated with reduced TNF-α-induced ICAM-1 levels, which is consistent with that induced by silibinin treatment. Taken together, silibinin inhibits ICAM-1 expression and its function through altered O-linked glycosylation in NF-κB and STAT1 signaling pathways and decreases the N-linked glycosylation of ICAM-1 transmembrane protein in proinflammatory cytokine-stimulated ARPE-19 cells.

scholarly journals Antioxidant and Anti-Inflammatory Effects of Blueberry Anthocyanins on High Glucose-Induced Human Retinal Capillary Endothelial Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Wuyang Huang ◽  
Zheng Yan ◽  
Dajing Li ◽  
Yanhong Ma ◽  
Jianzhong Zhou ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
High Glucose ◽  
Vascular Endothelial Cell ◽  
Intercellular Adhesion Molecule ◽  
Vascular Endothelial ◽  
Intercellular Adhesion Molecule 1 ◽  
Eye Health ◽  
Retinal Capillary ◽  
Capillary Endothelial Cells ◽  
Anti Inflammatory

Blueberries possess abundant anthocyanins, which benefit eye health. The purpose of this study was to explore the protective functional role of blueberry anthocyanin extract (BAE) and its predominant constituents, malvidin (Mv), malvidin-3-glucoside (Mv-3-glc), and malvidin-3-galactoside (Mv-3-gal), on high glucose- (HG-) induced injury in human retinal capillary endothelial cells (HRCECs). The results showed that BAE, Mv, Mv-3-glc, and Mv-3-gal enhanced cell viability (P<0.05 versus the HG group at 24 h); decreased the reactive oxygen species (ROS, P<0.01 versus the HG group both at 24 and 48 h); and increased the enzyme activity of catalase (CAT) and superoxide dismutase (SOD) (P<0.05 versus the HG group both at 24 and 48 h). Mv could greatly inhibit HG-induced Nox4 expression both at 24 and 48 h (P<0.05), while BAE and Mv-3-gal downregulated Nox4 only at 48 h (P<0.05). Mv, Mv-3-glc, and Mv-3-gal also changed nitric oxide (NO) levels (P<0.05). BAE and Mv-3-glc also influenced angiogenesis by decreasing the vascular endothelial cell growth factor (VEGF) level and inhibiting Akt pathway (P<0.05). Moreover, Mv and Mv-3-glc inhibited HG-induced intercellular adhesion molecule-1 (ICAM-1, P<0.001) and nuclear factor-kappa B (NF-κB) (P<0.05). It indicated that blueberry anthocyanins protected HRCECs via antioxidant and anti-inflammatory mechanisms, which could be promising molecules for the development of nutraceuticals to prevent diabetic retinopathy.

scholarly journals Danhong Huayu Koufuye Prevents Diabetic Retinopathy in Streptozotocin-Induced Diabetic Rats via Antioxidation and Anti-Inflammation

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Wenpei Chen ◽  
Xiaolan Yao ◽  
Chenghao Zhou ◽  
Ziyang Zhang ◽  
Gang Gui ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Serum Levels ◽  
Diabetic Rats ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Blood Retinal Barrier ◽  
Anti Inflammatory ◽  
Induced Apoptosis ◽  
Endothelial Growth Factor ◽  
Anti Inflammation

Danhong Huayu Koufuye (DHK), a traditional Chinese prescription, is used to treat central retinal vein occlusion clinically. We previously reported that DHK prevented diabetic retinopathy (DR) in rats. Moreover, we found that it protected endothelial cells from hyperglycemia-induced apoptosis through antioxidation and anti-inflammation. Here, we investigated whether antioxidative and anti-inflammatory activities of DHK contributed to its therapeutic effect on DR in streptozotocin- (STZ-) induced diabetic rats. DHK significantly blocked the breakdown of the blood-retinal barrier (BRB) and increased the thickness of the inner nuclear layer (INL), as well as suppressed the swelling of the ganglion cell layer (GCL) in diabetic retinas. DHK remarkably increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in plasma, and decreased serum level of nitric oxide (NO). Moreover, DHK markedly reduced the serum levels of vascular endothelial growth factor (VEGF) and intercellular adhesion molecule-1 (ICAM-1). Furthermore, DHK significantly downregulated protein expressions of VEGF and inducible NO synthase (iNOS) and mRNA expression of ICAM-1 in retinas. These results suggest that the antioxidative and anti-inflammatory activities of DHK may be important mechanisms involved in the protective effect of DHK on DR in STZ-induced diabetic rats.

Abstract 11678: Mitochondrial Reactive Oxygen Species Mediate Lysophosphatidylcholine-Induced Endothelial Cell Activation

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Xinyuan Li ◽  
Pu Fang ◽  
Ya-Feng Li ◽  
Yin-Ming Kuo ◽  
Andrew J Andrews ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cell Activation ◽  
Nuclear Translocation ◽  
Fluorescence Probe ◽  
Vascular Inflammation ◽  
Intercellular Adhesion Molecule ◽  
Mitochondrial Calcium ◽  
Activator Protein 1 ◽  
Intercellular Adhesion Molecule 1 ◽  
Endothelial Cell Activation

Background: Lysophosphatidylcholines (LPCs) are a class of pro-inflammatory lipids that play important roles in atherogenesis. LPC activates endothelial cells (ECs) to upregulate adhesion molecules and chemokines, which is the initiation step of atherogenesis. However, the mechanisms underlying LPC-triggered EC activation are not fully understood. Previously considered as the toxic by-products of cellular metabolism, mitochondrial ROS (mtROS) are recently found to directly contribute to both the innate and adaptive immune responses. Here we tested a novel hypothesis that mtROS serve as signaling mediators for LPC-induced EC activation. Methods and Results: Using electron spin resonance and flow cytometry with fluorescence probe MitoSOX, we found that several LPC species including LPC 16:0, 18:0, and 18:1 induced mtROS in human primary aortic ECs (HAECs). Mechanistically, our analysis using mitochondrial calcium inhibitor and Seahorse XF96 mitochondrial function analyzer showed that LPC induced mtROS via increasing mitochondrial calcium entry which resulted in mitochondrial proton leakage. In addition, we found that mtROS scavenger MitoTEMPO abolished LPC-induced EC activation by downregulating Intercellular adhesion molecule 1 (ICAM-1) and Vascular cell adhesion protein 1 (VCAM-1) in HAECs. Moreover, our analysis with transcription factor profiling screening showed that MitoTEMPO acts by blocking LPC-induced nuclear translocation of pro-inflammatory transcription factor activator protein-1 (AP-1). Conclusions: Our results indicate that mtROS are responsible for LPC-induced EC activation and that mtROS may serve as a novel therapeutic target for vascular inflammation.

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