Tanshinone IIA Ameliorates Inflammation Response in Osteoarthritis via Inhibition of miR-155/FOXO3 Axis

Pharmacology ◽  
2021 ◽  
pp. 1-9
Author(s):  
Biao Zhou ◽  
Lin-Hui Li ◽  
Li-Ming Tan ◽  
Wen-Bing Luo ◽  
Hui Xiong ◽  
...  
Keyword(s):  
Cell Apoptosis ◽  
Articular Chondrocytes ◽  
Inflammatory Responses ◽  
Joint Destruction ◽  
Annexin V ◽  
Tanshinone Iia ◽  
Therapeutic Drug ◽  
Inflammation Response ◽  
Tnf Α ◽  
Novel Therapeutic Strategies

<b><i>Background:</i></b> Osteoarthritis (OA) is the most common joint disorder characterized by degeneration of the articular cartilage and joint destruction with an associated risk of mobility disability in elderly people. Although a lot of achievements have been made, OA is still regarded as an incurable disease. Therefore, the pathological mechanisms and novel therapeutic strategies of OA need more investigation. <b><i>Methods:</i></b> MTT assay was conducted to measure the viability of chondrocytes after LPS treatment. Cell apoptosis was analyzed by annexin V/propidium iodide labeling. ELISA was used to determine the concentrations of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in the culture supernatant of chondrocytes. The expression level of miR-155, IL-1β, FOXO3, TNF-α, IL-6, caspase-3, and caspase-9 in chondrocytes was analyzed by RT-qPCR or Western blot. <b><i>Results:</i></b> We found that LPS led to inflammatory responses, cell apoptosis, and increased miR-155 expression in human articular chondrocytes. Tanshinone IIA could inhibit LPS-induced inflammation and cell apoptosis of chondrocytes via regulating the expression of miR-155 and FOXO3. miR-155 directly targeted the 3′-UTR of FOXO3 to regulate its expression. <b><i>Conclusions:</i></b> Taken together, our data suggest tanshinone IIA ameliorates inflammation response in OA via inhibition of the miR-155/FOXO3 axis, and provide some evidences that tanshinone IIA could be designed and developed as a new promising clinical therapeutic drug for OA patients.

scholarly journals Repurposing of Pirfenidone (Anti-Pulmonary Fibrosis Drug) for Treatment of Rheumatoid Arthritis

2021 ◽  
Vol 12 ◽  
Author(s):  
Donghao Gan ◽  
Wenxiang Cheng ◽  
Liqing Ke ◽  
Antonia RuJia Sun ◽  
Qingyun Jia ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Articular Chondrocytes ◽  
Joint Destruction ◽  
Pathological Process ◽  
Therapeutic Drug ◽  
Pathological Changes ◽  
Synovial Hyperplasia ◽  
Tnf Α ◽  
And Migration

Clinical studies have shown that pirfenidone (PFD) effectively relieves joint pain in rheumatoid arthritis (RA) patients. However, the detailed mechanisms underlying the anti-RA effects of PFD have not been investigated. This study was undertaken to investigate the repurposing of PFD for the treatment of RA, and explore its anti-rheumatic mechanisms. A collagen-induced arthritis (CIA) rat model was used to observe joint pathological changes following PFD treatment. Based on bioinformatics to predict the mechanism of PFD anti-RA, using EA. hy926 and TNF-α-induced MH7A cells to establish in vitro model to explore its biological mechanism from the perspectives of synovial inflammation and angiogenesis. PFD significantly relieved pathological changes, including joint swelling, synovial hyperplasia, inflammatory cell infiltration and joint destruction. PFD was also associated with reduced expression of MMP-3 and VEGF in articular chondrocytes and synovial cells of CIA rats (p &lt; 0.05). Using bioinformatic methods, we predicted that PFD inhibits cell inflammation and migration by interfering with the JAK2/STAT3 and Akt pathways. These results were verified using in vitro models. In particular, PFD effectively reduced the expression of pro-inflammatory, chondrogenic, and angiogenic cytokines, such as IL-1β, IL-6, IL-8, MMP-1/3/2/9 and VEGF (p &lt; 0.05), in TNF-α-induced MH7A cells. In addition, PFD significantly reduced the production of MMP-2/9 and VEGF in EA. hy926 cells, thereby weakening migration and inhibiting angiogenesis (p &lt; 0.05). These findings suggest that PFD may alleviate the pathological process in CIA rats, by inhibiting inflammation and angiogenesis through multiple pathways, and serve as a potential therapeutic drug for RA.

scholarly journals Endosulfan Increases IL-1β, IL-6, IL-17, and TNF-α Production in Pregnant Rats and Causes Fetal Brain Cell Apoptosis

2019 ◽  
Vol 17 (2) ◽  
pp. 103-112
Author(s):  
Sri ANDARINI ◽  
Asmika MADJRI ◽  
Hidayat SUJUTI ◽  
Romi ROMI ◽  
Adi Surya PRATAMA ◽  
...  
Keyword(s):  
Cell Apoptosis ◽  
Organic Pollutant ◽  
Fetal Brain ◽  
Annexin V ◽  
Negative Control ◽  
Brain Cell ◽  
Rat Serum ◽  
Pregnant Rats ◽  
Group I ◽  
Tnf Α

Endosulfan is a persistent organic pollutant commonly used as an insecticide in Indonesia. It has been reported to cause teratogenic effects, i.e., to decrease humoral activity, produce inflammation, and induce apoptosis in various type of cells. This study investigated the effect of endosulfan on the expression of IL-1β, IL-6, IL-17, and TNF-α in rats (Rattus norvegicus), as well as the incidence of fetal brain cell apoptosis. This experiment was carried out on pregnant rats divided into 4 groups: negative control (I), endosulfan: 1 mg/kg (II), 10 mg/kg (III), and 50 mg/kg (IV). The solution of endosulfan was given daily during the 20-day test period. Rat serum was collected for the measurement of IL-1β, IL-6, IL-17, and TNF-α using the ELISA kit. Fetal rat brains were taken and stained with Annexin V for apoptosis detection. The proinflammatory cytokine levels in Groups II, III, and IV were higher than in Group I, with significant increases of IL-1β (p = 0.016), IL-6 (p = 0.009), IL-17 (p < 0.001), and TNF-α (p < 0.001). The intensity of Annexin V in 4 groups of rats showed that the incidence of apoptosis increased with increasing endosulfan doses. In conclusion, the administration of endosulfan in pregnant rats increased the expression of IL-1β, IL-6, IL-17, and TNF-α and triggered apoptosis in fetal brain cells.

scholarly journals Concentration-Dependent Effects of Cobalt and Chromium Ions on Osteoarthritic Chondrocytes

Cartilage ◽  
2019 ◽  
pp. 194760351988938
Author(s):  
Christoph Bauer ◽  
Christoph Stotter ◽  
Vivek Jeyakumar ◽  
Eugenia Niculescu-Morzsa ◽  
Bojana Simlinger ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Metabolic Activity ◽  
Transcriptional Activity ◽  
Articular Chondrocytes ◽  
Inflammatory Responses ◽  
Quantitative Polymerase Chain Reaction ◽  
Human Articular Chondrocytes ◽  
Tnf Α ◽  
Late Apoptosis ◽  
Pro Inflammatory Cytokines

Objective Cobalt and chromium (CoCr) ions from metal implants are released into the joint due to biotribocorrosion, inducing apoptosis and altering gene expression in various cell types. Here, we asked whether CoCr ions concentration-dependently changed viability, transcriptional activity, and inflammatory response in human articular chondrocytes. Design Human articular chondrocytes were exposed to Co (1.02-16.33 ppm) and Cr (0.42-6.66 ppm) ions and cell viability and early/late apoptosis (annexin V and 7-AAD) were assessed in 2-dimensional cell cultures using the XTT assay and flow cytometry, respectively. Changes in chondrocyte morphology were assessed using transmitted light microscopy. The effects of CoCr ions on transcriptional activity of chondrocytes were evaluated by quantitative polymerase chain reaction (qPCR). The inflammatory responses were determined by measuring the levels of released pro-inflammatory cytokines (interleukin-1β [IL-1β], IL-6, IL-8, and tumor necrosis factor–α [TNF-α]). Results CoCr ions concentration-dependently reduced metabolic activity and induced early and late apoptosis after 24 hours in culture. After 72 hours, the majority of chondrocytes (>90%) were apoptotic at the highest concentrations of CoCr ions (16.33/6/66 ppm). SOX9 expression was concentration-dependently enhanced, whereas expression of COL2A1 linearly decreased after 24 hours. IL-8 release was enhanced proportionally to CoCr ions levels, whereas IL-1β, IL-6, and TNF-α levels were not affected by the treatments. Conclusions CoCr ions showed concentration- and time-dependent effects on articular chondrocytes. Fractions of apoptotic articular chondrocytes were proportional to CoCr ion concentrations. In addition, metabolic activity and expression of chondrocyte-specific genes were decreased by CoCr ions. Furthermore, exposure to CoCr ions caused a release of pro-inflammatory cytokines.

scholarly journals FM0807 decelerates experimental arthritis progression by inhibiting inflammatory responses and joint destruction via modulating NF-κB and MAPK pathways

2019 ◽  
Vol 39 (9) ◽  
Author(s):  
Nanwen Zhang ◽  
Zhiwei Liu ◽  
Hongbin Luo ◽  
Weifang Wu ◽  
Kaimei Nie ◽  
...  
Keyword(s):  
Synovial Fluid ◽  
Inflammatory Responses ◽  
Mapk Pathway ◽  
Joint Destruction ◽  
Mitogen Activated Protein Kinase ◽  
Inflammatory Factors ◽  
Enzyme Linked Immunosorbent Assay ◽  
Therapeutic Effects ◽  
Dependent Manner ◽  
Tnf Α

Abstract Background: Rheumatoid arthritis (RA) is a chronic articular synovial inflammatory disease. The precise etiology underlying the pathogenesis of RA remains unknown. We aimed to investigate the inhibitory effect of curcumin analog FM0807 (curcumin salicylate monoester, 2-hydroxy-, 4-[(1E,6E)-7-(4-hydroxy-3-methoxyphenyl)-3,5-dioxo-1,6-heptadien-1-yl]-2-methoxyphenyl ester) on experimental RA and investigate its possible mechanisms of action. Method: Rats with Freund’s complete adjuvant (FCA)-induced arthritis (AIA) were administered aspirin (0.1 mmol.kg−1), curcumin (0.1 mmol.kg−1), FM0807 (0.1, 0.2 mmol.kg−1) and vehicle via gastric gavage, from days 7 to 21, once daily. The hind paw volume and arthritis index (AI) were measured, and radiographic and histological examinations were performed. Twenty-one days later, the animals were killed and left ankle joints were removed to measure protein expression of the elements of the nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathway by Western blot analysis. The enzyme-linked immunosorbent assay (ELISA) was employed to measure synovial fluid levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-1β and IL-10. Results: Compared with AIA group, FM0807 reduced the AI and swelling of the injected hind paw in a dose-dependent manner, and inhibited increases in inflammatory cell infiltration, pannus formation and cartilage destruction. FM0807 also potently attenuated the increase in the expression of inflammatory factors TNF-α, IL-6 and IL-1β in synovial fluid, while IL-10 levels were also elevated. FM0807 significantly suppressed phosphorylation of extracellular-signal-regulated kinase (ERK) 1/2 (ERK1/2), c-Jun-N-terminal kinase (JNK) 1/2 (JNK1/2), p38MAPK, inhibitor of NF-κB kinase (IKK), IκB and NF-κB p65 protein, (all P<0.05), which displayed more potential effects compared with those of the aspirin and curcumin groups. Conclusion: FM0807 exerts its therapeutic effects on RA by inhibiting cartilage degeneration. FM0807 treatment might be an effective therapeutic approach for RA.

scholarly journals MicroRNA-181c Inhibits Interleukin-6-mediated Beta Cell Apoptosis by Targeting TNF-α Expression

Molecules ◽  
2019 ◽  
Vol 24 (7) ◽  
pp. 1410 ◽  
Author(s):  
Yoon Sin Oh ◽  
Gong Deuk Bae ◽  
Eun-Young Park ◽  
Hee-Sook Jun
Keyword(s):  
Beta Cell ◽  
Mrna Expression ◽  
Beta Cells ◽  
Interleukin 6 ◽  
Cell Apoptosis ◽  
Neutralizing Antibodies ◽  
Annexin V ◽  
Beta Cell Apoptosis ◽  
Tnf Α ◽  
Long Term Treatment

We have previously reported that long-term treatment of beta cells with interleukin-6 (IL-6) is pro-apoptotic. However, little is known about the regulatory mechanisms that are involved. Therefore, we investigated pro-apoptotic changes in mRNA expression in beta cells in response to IL-6 treatment. We analyzed a microarray with RNA from INS-1 beta cells treated with IL-6, and found that TNF-α mRNA was significantly upregulated. Inhibition of TNF-α expression by neutralizing antibodies significantly decreased annexin V staining in cells compared with those treated with a control antibody. We identified three microRNAs that were differentially expressed in INS-1 cells incubated with IL-6. In particular, miR-181c was significantly downregulated in IL-6-treated cells compared with control cells and the decrease of miR-181c was attenuated by STAT-3 signaling inhibition. TNF-α mRNA was a direct target of miR-181c and upregulation of miR-181c by mimics, inhibited IL-6-induced increase in TNF-α mRNA expression. Consequently, reduction of TNF-α mRNA caused by miR-181c mimics enhanced cell viability in IL-6 treated INS-1 cells. These results demonstrated that miR-181c regulation of TNF-α expression plays a role in IL-6-induced beta cell apoptosis.

scholarly journals The Liver Protection Effects of Maltol, a Flavoring Agent, on Carbon Tetrachloride-Induced Acute Liver Injury in Mice via Inhibiting Apoptosis and Inflammatory Response

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2120 ◽  
Author(s):  
Wei Liu ◽  
Zi Wang ◽  
Jin-gang Hou ◽  
Yan-dan Zhou ◽  
Yu-fang He ◽  
...  
Keyword(s):  
Carbon Tetrachloride ◽  
Liver Injury ◽  
Cell Apoptosis ◽  
Inflammatory Responses ◽  
Histopathological Examination ◽  
Single Agent ◽  
Nuclear Condensation ◽  
Sod Activity ◽  
Tnf Α

The purpose of this research was to evaluate whether maltol could protect from hepatic injury induced by carbon tetrachloride (CCl4) in vivo by inhibition of apoptosis and inflammatory responses. In this work, maltol was administered at a level of 100 mg/kg for 15 days prior to exposure to a single injection of CCl4 (0.25%, i.p.). The results clearly indicated that the intrapulmonary injection of CCl4 resulted in a sharp increase in serum aspartate transaminase (AST) and alanine transaminase (ALT) activities, tumor necrosis factor-α (TNF-α), irreducible nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-κB) and interleukin-1β (IL-1β) levels. Histopathological examination demonstrated severe hepatocyte necrosis and the destruction of architecture in liver lesions. Immunohistochemical staining and western blot analysis suggested an accumulation of iNOS, NF-κB, IL-1β and TNF-α expression. Maltol, when administered to mice for 15 days, can significantly improve these deleterious changes. In addition, TUNEL and Hoechst 33258 staining showed that a liver cell nucleus of a model group diffused uniform fluorescence following CCl4 injection. Maltol pretreatment groups did not show significant cell nuclear condensation and fragmentation, indicating that maltol inhibited CCl4-induced cell apoptosis. By evaluating the liver catalase (CAT), glutathione (GSH), superoxide dismutase (SOD) activity, and further using a single agent to evaluate the oxidative stress in CCl4-induced hepatotoxicity by immunofluorescence staining, maltol dramatically attenuated the reduction levels of hepatic CAT, GSH and SOD, and the over-expression levels of CYP2E1 and HO-1. In the mouse model of CCl4-induced liver injury, we have demonstrated that the inflammatory responses were inhibited, the serum levels of ALT and AST were reduced, cell apoptosis was suppressed, and liver injury caused by CCl4 was alleviated by maltol, demonstrating that maltol may be an efficient hepatoprotective agent.

scholarly journals Camostat mesilate inhibits pro-inflammatory cytokine secretion and improves cell viability by regulating MFGE8 and HMGN1 in lipopolysaccharide-stimulated DF-1 chicken embryo fibroblasts

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12053
Author(s):  
Lin Yuan ◽  
Mengjie Li ◽  
Zhishuai Zhang ◽  
Wanli Li ◽  
Wei Jin ◽  
...  
Keyword(s):  
Cell Viability ◽  
Cell Apoptosis ◽  
Chicken Embryo ◽  
Inflammatory Responses ◽  
Proteomics Analysis ◽  
Camostat Mesilate ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Embryo Fibroblasts ◽  
Chicken Embryo Fibroblasts

Camostat mesilate (CM) possesses potential anti-viral and anti-inflammatory activities. However, it remains unknown whether CM is involved in lipopolysaccharide (LPS)-mediated inflammatory responses and cell injury. In this project, differentially expressed proteins (DEPs, fold change ≥ 1.2 or ≤ 0.83 and Q value ≤ 0.05) in response to LPS stimulation alone or in combination with CM were identified through tandem mass tags (TMT)/mass spectrometry (MS)-based proteomics analysis in DF-1 chicken embryo fibroblasts. The mRNA expression levels of filtered genes were determined by RT-qPCR assay. The results showed that CM alleviated the detrimental effect of LPS on cell viability and inhibited LPS-induced TNF-α and IL-6 secretions in DF-1 chicken embryo fibroblasts. A total of 141 DEPs that might be involved in mediating functions of both LPS and CM were identified by proteomics analysis in DF-1 chicken embryo fibroblasts. LPS inhibited milk fat globule EGF and factor V/VIII domain containing (MFGE8) expression and induced high mobility group nucleosome binding domain 1 (HMGN1) expression, while these effects were abrogated by CM in DF-1 chicken embryo fibroblasts. MFGE8 knockdown facilitated TNF-α and IL-6 secretions , reduced cell viability, stimulated cell apoptosis in DF-1 chicken embryo fibroblasts co-treated with LPS and CM. HMGN1 loss did not influence TNF-α and IL-6 secretions, cell viability, and cell apoptosis in DF-1 chicken embryo fibroblasts co-treated with LPS and CM. In conclusion, CM exerted anti-inflammatory and pro-survival activities by regulating MFGE8 in LPS-stimulated DF-1 chicken embryo fibroblasts, deepening our understanding of the roles and molecular basis of CM in protecting against Gram-negative bacteria.

scholarly journals MicroRNA miR-27b-3p regulate microglial inflammation response and cell apoptosis by inhibiting A20 (TNF-α-induced protein 3)

Bioengineered ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 9902-9913
Author(s):  
Liping Li ◽  
Chao Qi ◽  
Yuanyuan Liu ◽  
Youliang Shen ◽  
Xia Zhao ◽  
...  
Keyword(s):  
Cell Apoptosis ◽  
Inflammation Response ◽  
Tnf Α ◽  
Microglial Inflammation

Anti-β2 Glycoprotein I Antibodies Cause Inflammation and Recruit Dendritic Cells in Platelet Clearance

2001 ◽  
Vol 86 (11) ◽  
pp. 1257-1263 ◽  
Author(s):  
Attilio Bondanza ◽  
Angelo Manfredi ◽  
Valérie Zimmermann ◽  
Matteo Iannacone ◽  
Angela Tincani ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Inflammatory Responses ◽  
Glycoprotein I ◽  
Activated Platelets ◽  
Tnf Α ◽  
Per Se ◽  
Antigen Presenting ◽  
Antiinflammatory Cytokine

SummaryScavenger phagocytes are mostly responsible for the in vivo clearance of activated or senescent platelets. In contrast to other particulate substrates, the phagocytosis of platelets does not incite pro-inflammatory responses in vivo. This study assessed the contribution of macrophages and dendritic cells (DCs) to the clearance of activated platelets. Furthermore, we verified whether antibodies against the β2 Glycoprotein I (β2GPI), which bind to activated platelets, influence the phenomenon. DCs did not per se internalise activated platelets. In contrast, macrophages efficiently phagocytosed platelets. In agreement with the uneventful nature of the clearance of platelets in vivo, phagocytosing macrophages did not release IL-1β, TNF-α or IL-10. β2GPI bound to activated platelets and was required for their recognition by anti-ββ2GPI antibodies. DCs internalised platelets opsonised by anti-ββ2GPI antibodies. The phagocytosis of opsonised platelets determined the release of TNF-α and IL-1β by DCs and macrophages. Phagocytosing macrophages, but not DCs, secreted the antiinflammatory cytokine IL-1β0. We conclude that anti-ββ2GPI antibodies cause inflammation during platelet clearance and shuttle platelet antigens to antigen presenting DCs.

scholarly journals Punicalagin Prevents Inflammation in LPS-Induced RAW264.7 Macrophages by Inhibiting FoxO3a/Autophagy Signaling Pathway

Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2794 ◽  
Author(s):  
Cao ◽  
Chen ◽  
Ren ◽  
Zhang ◽  
Tan ◽  
...  
Keyword(s):  
Western Blot ◽  
Signaling Pathway ◽  
Inflammatory Cytokines ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Inflammatory Responses ◽  
Raw264.7 Macrophages ◽  
Tnf Α ◽  
Autophagy Inhibition ◽  
Pro Inflammatory Cytokines

Punicalagin, a hydrolysable tannin of pomegranate juice, exhibits multiple biological effects, including inhibiting production of pro-inflammatory cytokines in macrophages. Autophagy, an intracellular self-digestion process, has been recently shown to regulate inflammatory responses. In this study, we investigated the anti-inflammatory potential of punicalagin in lipopolysaccharide (LPS) induced RAW264.7 macrophages and uncovered the underlying mechanisms. Punicalagin significantly attenuated, in a concentration-dependent manner, LPS-induced release of NO and decreased pro-inflammatory cytokines TNF-α and IL-6 release at the highest concentration. We found that punicalagin inhibited NF-κB and MAPK activation in LPS-induced RAW264.7 macrophages. Western blot analysis revealed that punicalagin pre-treatment enhanced LC3II, p62 expression, and decreased Beclin1 expression in LPS-induced macrophages. MDC assays were used to determine the autophagic process and the results worked in concert with Western blot analysis. In addition, our observations indicated that LPS-induced releases of NO, TNF-α, and IL-6 were attenuated by treatment with autophagy inhibitor chloroquine, suggesting that autophagy inhibition participated in anti-inflammatory effect. We also found that punicalagin downregulated FoxO3a expression, resulting in autophagy inhibition. Overall these results suggested that punicalagin played an important role in the attenuation of LPS-induced inflammatory responses in RAW264.7 macrophages and that the mechanisms involved downregulation of the FoxO3a/autophagy signaling pathway.

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