scholarly journals MicroRNA-181a-5p regulates inflammatory response of macrophages in sepsis

Open Medicine ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. 899-908 ◽  
Author(s):  
Zheng Huang ◽  
Hang Xu
Keyword(s):  
Inflammatory Response ◽  
Inflammatory Cytokines ◽  
Sirtuin 1 ◽  
Raw 264.7 Cells ◽  
Inflammatory Factors ◽  
Raw 264.7 ◽  
Raw264.7 Macrophages ◽  
Pathway Activation

AbstractThe aim of this study was to evaluate the role of miR-181a-5p in sepsis, and to further explore the molecular mechanism. RAW 264.7 cells were stimulated with 1 μg/ml LPS for 4 hours. Firstly, qRT-PCR and ELISA was adopted to evaluate the expression of miR-181a-5p and p ro-inflammatory cytokines in RAW 264.7 macrophages a fter LPS stimulation. Results showed that pro-inflammatory cytokines and miR-181a-5p were significantly increased after LPS treatment. Then, we identified that sirtuin-1 (SIRT1) was a direct target of miR-181a-5p and it was down-regulated in LPS treated RAW264.7 macrophages. Furthermore, the data suggested that the miR-181a-5p inhibitor significantly inhibited LPS enhanced inflammatory cytokines expression and NF-κB pathway activation, and these changes were eliminated by SIRT1 silencing. Moreover, the role of the miR-181a-5p inhibitor on sepsis was studied in vivo. We found that the miR-181a-5p inhibitor significantly decreased the secretion of inflammatory factors, and the levels of creatine (Cr), blood urea nitrogen (BUN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in a serum for mice with sepsis. However, all the effects were reversed by SIRT1-siRNA. In summary, these results indicated that miR-181a-5p was involved in sepsis through regulating the inflammatory response by targeting SIRT1, suggesting that miR-181a-5p may be a potential target for the treatment of sepsis.

scholarly journals Expression and role of ABIN1 in sepsis: In vitro and in vivo studies

Open Medicine ◽  
2020 ◽  
Vol 16 (1) ◽  
pp. 033-040
Author(s):  
Haolan Li ◽  
Aichen Sun ◽  
Taocheng Meng ◽  
Yan Zhu
Keyword(s):  
Inflammatory Response ◽  
Molecular Mechanisms ◽  
Organ Injury ◽  
In Vivo Studies ◽  
Inflammatory Factors ◽  
Septic Mouse ◽  
Raw264.7 Macrophages ◽  
Tnf Α

AbstractIn this research, we attempted to explain the effect and the related molecular mechanisms of ABIN1 in lipopolysaccharide (LPS)-induced septic mice or RAW264.7 macrophages. LPS was adopted to treat RAW264.7 macrophages for 4 h, and the levels of inflammatory factors were assessed by ELISA. Besides, ABIN1 expression was measured by quantitative reverse transcription polymerase chain reaction. Apparently, LPS enhanced immunoreaction, suggested by increased expression of IL-1β, tumor necrosis factor (TNF)-α, and IL-6. ABIN1 levels were obviously reduced compared to the control. Furthermore, we evaluated the roles of ABIN1-plasmid in immunoreaction and nuclear factor-κB (NF-κB) pathway. We found that ABIN1-plasmid significantly reduced the expression of IL-1β, TNF-α, and IL-6 in LPS-treated cells and inhibited NF-κB pathway activation. Meanwhile, a septic mouse mode was conducted to validate the role of ABIN1 in inflammatory response and organ damage in vivo. These data suggested that ABIN1-plasmid significantly inhibited the secretion of inflammatory cytokines and Cr, BUN, AST, and ALT levels in the serum of LPS-stimulated mice compared to LPS + control-plasmid group, reflecting the relieved inflammation and organ injury. In summary, the present findings indicated that ABIN1 alleviated sepsis by repressing inflammatory response through NF-κB signaling pathway, emphasizing the potential value of ABIN1 as therapeutic strategy for sepsis.

scholarly journals Phaseolin Attenuates Lipopolysaccharide-Induced Inflammation in RAW 264.7 Cells and Zebrafish

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 420
Author(s):  
Su-Jung Hwang ◽  
Ye-Seul Song ◽  
Hyo-Jong Lee
Keyword(s):  
Nitric Oxide ◽  
Nuclear Translocation ◽  
Raw 264.7 Cells ◽  
Network Pharmacology ◽  
Raw 264.7 ◽  
Dependent Manner ◽  
Bioactive Constituents

Kushen (Radix Sophorae flavescentis) is used to treat ulcerative colitis, tumors, and pruritus. Recently, phaseolin, formononetin, matrine, luteolin, and quercetin, through a network pharmacology approach, were tentatively identified as five bioactive constituents responsible for the anti-inflammatory effects of S. flavescentis. However, the role of phaseolin (one of the primary components of S. flavescentis) in the direct regulation of inflammation and inflammatory processes is not well known. In this study, the beneficial role of phaseolin against inflammation was explored in lipopolysaccharide (LPS)-induced inflammation models of RAW 264.7 macrophages and zebrafish larvae. Phaseolin inhibited LPS-mediated production of nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS), without affecting cell viability. In addition, phaseolin suppressed pro-inflammatory mediators such as cyclooxygenase 2 (COX-2), interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and interleukin-6 (IL-6) in a dose-dependent manner. Furthermore, phaseolin reduced matrix metalloproteinase (MMP) activity as well as macrophage adhesion in vitro and the recruitment of leukocytes in vivo by downregulating Ninjurin 1 (Ninj1), an adhesion molecule. Finally, phaseolin inhibited the nuclear translocation of nuclear factor-kappa B (NF-κB). In view of the above, our results suggest that phaseolin could be a potential therapeutic candidate for the management of inflammation.

scholarly journals RhTrx-1 ameliorates miroglial neuroinflammation after cerebral ischemic stroke

2020 ◽  
Author(s):  
Yang Jiao ◽  
Jianjian Wang ◽  
Huixue Zhang ◽  
Yuze Cao ◽  
Yang Qu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Inflammatory Response ◽  
Inflammatory Responses ◽  
Inflammatory Factors ◽  
Experimental Stroke ◽  
Inflammasome Activation ◽  
Cerebral Ischemic

Abstract Background Microglia are rapidly activated after ischemic stroke and participate in the occurrence of neuroinflammation, which exacerbates the injury of ischemic stroke. Receptor Interacting Serine Threonine Kinase 1 (RIPK1) is thought to be involved in the development of inflammatory responses, but its role in ischemic microglia remains unclear. Here, we applied recombinant human thioredoxin-1 (rhTrx-1), a potential neuroprotective agent, to explore the role of rhTrx-1 in inhibiting RIPK1-mediated neuroinflammatory responses in microglia. Method Middle cerebral artery occlusion (MCAO) and Oxygen and glucose deprivation (OGD) were conducted for in vivo and in vitro experimental stroke models. The expression of RIPK1 in microglia after ischemia was examined. The inflammatory response of microglia was analyzed after treatment with rhTrx-1 and Necrostatin-1 (Nec-1, inhibitors of RIPK1), and the mechanisms were explored. In addition, the effects of rhTrx-1 on neurobehavioral deficits and cerebral infarct volume were examined. Results RIPK1 expression was detected in microglia after ischemia. Molecular docking results showed that rhTrx-1 could directly bind to RIPK1. In vitro experiments found that rhTrx-1 reduced necroptosis, mitochondrial membrane potential damage, Reactive oxygen species (ROS) accumulation and NLR Family, pyrin domain-containing 3 protein (NLRP3) inflammasome activation by inhibiting RIPK-1 expression, and regulated microglial M1/M2 phenotypic changes, thereby reducing the release of inflammatory factors. Consistently, in vivo experiments found that rhTrx-1 treatment attenuated cerebral ischemic injury by inhibiting the inflammatory response. Conclusion Our study demonstrates the role of RIPK1 in microglia-arranged neuroinflammation after cerebral ischemia. Administration of rhTrx-1 provides neuroprotection in ischemic stroke-induced microglial neuroinflammation by inhibiting RIPK1 expression.

scholarly journals Mycolactone toxin induces an inflammatory response by targeting the IL-1β pathway: Mechanistic insight into Buruli ulcer pathophysiology

2020 ◽  
Vol 16 (12) ◽  
pp. e1009107
Author(s):  
M. Foulon ◽  
M. Robbe-Saule ◽  
J. Manry ◽  
L. Esnault ◽  
Y. Boucaud ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Buruli Ulcer ◽  
Mycobacterium Ulcerans ◽  
Inflammatory Factors ◽  
Dependent Manner ◽  
Local Inflammatory Response ◽  
Mechanistic Insight ◽  
Insight Into

Mycolactone, a lipid-like toxin, is the major virulence factor of Mycobacterium ulcerans, the etiological agent of Buruli ulcer. Its involvement in lesion development has been widely described in early stages of the disease, through its cytotoxic and immunosuppressive activities, but less is known about later stages. Here, we revisit the role of mycolactone in disease outcome and provide the first demonstration of the pro-inflammatory potential of this toxin. We found that the mycolactone-containing mycobacterial extracellular vesicles produced by M. ulcerans induced the production of IL-1β, a potent pro-inflammatory cytokine, in a TLR2-dependent manner, targeting NLRP3/1 inflammasomes. We show our data to be relevant in a physiological context. The in vivo injection of these mycolactone-containing vesicles induced a strong local inflammatory response and tissue damage, which were prevented by corticosteroids. Finally, several soluble pro-inflammatory factors, including IL-1β, were detected in infected tissues from mice and Buruli ulcer patients. Our results revisit Buruli ulcer pathophysiology by providing new insight, thus paving the way for the development of new therapeutic strategies taking the pro-inflammatory potential of mycolactone into account.

scholarly journals Anti-Inflammatory Effects of 6,7-Dihydroxy-4-Methylcoumarin on LPS-Stimulated Macrophage Phosphorylation in MAPK Signaling Pathways

2021 ◽  
Vol 16 (5) ◽  
pp. 1934578X2110209
Author(s):  
Yun Sil Kang ◽  
You Chul Chung ◽  
Jung No Lee ◽  
Bong Seok Kim ◽  
Chang-Gu Hyun
Keyword(s):  
Signaling Pathways ◽  
Inflammatory Cytokines ◽  
Inflammatory Diseases ◽  
Mapk Signaling ◽  
Raw 264.7 Cells ◽  
Inflammatory Factors ◽  
Raw 264.7 ◽  
Dependent Manner ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

Coumarin derivatives, such as esculetin, have various physiological functions, including antioxidant, anti-inflammatory, antibacterial, antiviral, and anti-cancer. 6,7-Dihydroxy-4-methylcoumarin (6,7-DH-4MC) is a derivative of esculetin, and its anti-inflammatory effect and mechanism in macrophages have not been studied. In this study, the anti-inflammatory activity of 6,7-DH-4MC was evaluated by measuring the expression of inflammatory factors (NO and PGE2) and pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) in LPS-stimulated RAW 264.7 macrophages. The results revealed that 6,7-DH-4MC significantly reduced NO levels and PGE2 expression without inducing cytotoxicity; it was confirmed that the inhibition of NO and PGE2 expression was related to iNOS and COX-2 downregulation in response to 6,7-DH-4MC treatment. Moreover, 6,7-DH-4MC decreased the levels of pro-inflammatory cytokines, such as IL-1β and IL-6, in a dose-dependent manner. Mechanistic studies revealed reduced phosphorylation of ERK and p38-MAPK upon 6,7-DH-4MC treatment. Furthermore, the degradation of IκB-α and phosphorylation of NF-κB in cells treated with LPS were interrupted by 6,7-DH-4MC treatment. These results suggest that 6,7-DH-4MC is a potential therapeutic agent for inflammatory diseases. To the best of our knowledge, this is the first report demonstrating the anti-inflammatory effects of 6,7-DH-4MC in RAW 264.7 cells via MAPK and NF-κB signaling pathways.

scholarly journals Isorhapontigenin from Traditionally used Iris Domestica Reduces the Inflammatory Response by Suppressing NF-κB and MAPK Signaling in LPS-Activated RAW 264.7 Macrophages

2021 ◽  
Author(s):  
Wen-Chung Huang ◽  
Shu-Ju Wu ◽  
Han Lo ◽  
Hui-Ling Peng ◽  
Sindy Hu ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Proinflammatory Cytokine ◽  
Protein Localization ◽  
Mapk Signaling ◽  
Raw 264.7 Cells ◽  
Heme Oxygenase 1 ◽  
Raw 264.7 ◽  
Western Blots ◽  
Pathway Activation ◽  
Species Production

Abstract BackgroundIsorhapontigenin, a resveratrol analogue, isolated from Iris domestica can induce apoptosis in tumor cells. Here, we designed to explore whether isorhapontigenin reduced inflammatory response in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells.MethodsIsorhapontigenin treated with RAW 264.7 cells, and then with LPS to stimulate inflammatory response. Proinflammatory cytokine expressions were measured using ELISA, and protein expressions were detected using western blots. ResultsIsorhapontigenin significantly inhibited the proinflammatory cytokine expressions. Isorhapontigenin also decreased cyclooxygenase-2 and inducible nitric oxide synthase productions and promoted heme oxygenase-1 expression in LPS-stimulated RAW264.7 cells. Isorhapontigenin could significantly inhibit NF-κB subunit p65 protein localization to the nucleus and reduced MAPK signal pathway activation. Isorhapontigenin also decreased reactive oxygen species production. ConclusionThus, isorhapontigenin has potential anti-inflammation and anti-oxidative stress that inhibits inflammatory mediators and cytokines expressions through suppressing the MAPK and NF-κB pathways.

scholarly journals BRD4 inhibition alleviates mechanical stress-induced TMJ OA-like pathological changes and attenuates TREM1-mediated inflammatory response

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Ziwei Huang ◽  
Ren Yang ◽  
Lu Zhang ◽  
Mengjiao Zhu ◽  
Caixia Zhang ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Mechanical Stress ◽  
Inflammatory Cytokines ◽  
Inflammatory Factors ◽  
Pathological Changes ◽  
Condylar Cartilage ◽  
Temporomandibular Joint Osteoarthritis ◽  
Brd4 Inhibition

AbstractThe aim of this paper was to investigate the protective effects of bromodomain containing 4 (BRD4) inhibition on the temporomandibular joint osteoarthritis (TMJ OA) induced by compressive mechanical stress and to explore the underlying mechanism. In vivo, a rat model of TMJ compressive loading device was used and BRD4 inhibitor was injected into the TMJ region. HE staining and micro-CT analysis were used for histological and radiographic assessment. Immunohistochemistry and qPCR were performed to detect inflammatory cytokines expressions. High-throughput ChIP-sequencing screening was performed to compare the BRD4 and H3K27ac binding patterns between condylar cartilage from control and mechanical force groups. In vitro, the mandibular condylar chondrocytes were treated with IL-1β. Small Interference RNA (siRNA) infection was used to silencing BRD4 or TREM1. qPCR was performed to detect inflammatory cytokines expressions. Our study showed that BRD4 inhibition can alleviate the thinning of condylar cartilage and subchondral bone resorption, as well as decrease the inflammatory factors expression both in vivo and in vitro. ChIP-seq analysis showed that BRD4 was more enriched in the promoter region of genes related to the stress and inflammatory pathways under mechanical stress in vivo. Trem1, a pro-inflammatory gene, was screened out from the overlapped BRD4 and H3K27ac increased binding sites, and Trem1 mRNA was found to be regulated by BRD4 inhibition both in vivo and in vitro. TREM1 inhibition reduced the expression of inflammatory factors induced by IL-1β in vitro. In summary, we concluded that BRD4 inhibition can protect TMJ OA-like pathological changes induced by mechanical stress and attenuate TREM1-mediated inflammatory response.

scholarly journals Stevioside Activates AMPK to Suppress Inflammation in Macrophages and Protects Mice from LPS-Induced Lethal Shock

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 858
Author(s):  
Fuyao Wei ◽  
Hong Zhu ◽  
Na Li ◽  
Chunlei Yu ◽  
Zhenbo Song ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Mononuclear Cells ◽  
Inflammatory Responses ◽  
Raw 264.7 Cells ◽  
Inflammatory Factors ◽  
Enhanced Production ◽  
Lethal Shock ◽  
Anti Inflammatory

Stevioside, a diterpenoid glycoside, is widely used as a natural sweetener; meanwhile, it has been proven to possess various pharmacological properties as well. However, until now there were no comprehensive evaluations focused on the anti-inflammatory activity of stevioside. Thus, the anti-inflammatory activities of stevioside, both in macrophages (RAW 264.7 cells, THP-1 cells, and mouse peritoneal macrophages) and in mice, were extensively investigated for the potential application of stevioside as a novel anti-inflammatory agent. The results showed that stevioside was capable of down-regulating lipopolysaccharide (LPS)-induced expression and production of pro-inflammatory cytokines and mediators in macrophages from different sources, such as IL-6, TNF-α, IL-1β, iNOS/NO, COX2, and HMGB1, whereas it up-regulated the anti-inflammatory cytokines IL-10 and TGF-β1. Further investigation showed that stevioside could activate the AMPK -mediated inhibition of IRF5 and NF-κB pathways. Similarly, in mice with LPS-induced lethal shock, stevioside inhibited release of pro-inflammatory factors, enhanced production of IL-10, and increased the survival rate of mice. More importantly, stevioside was also shown to activate AMPK in the periphery blood mononuclear cells of mice. Together, these results indicated that stevioside could significantly attenuate LPS-induced inflammatory responses both in vitro and in vivo through regulating several signaling pathways. These findings further strengthened the evidence that stevioside may be developed into a therapeutic agent against inflammatory diseases.

Extraction, Characterization and Immunological Activity of Polysaccharides from Cynomorium songaricum Rupr.

2021 ◽  
Vol 11 (8) ◽  
pp. 1543-1554
Author(s):  
Min Li ◽  
Jianhua Yang ◽  
Junping Hu
Keyword(s):  
Inflammatory Cytokines ◽  
Phagocytic Activity ◽  
Active Component ◽  
Immunomodulatory Activity ◽  
Immunological Activity ◽  
Raw264.7 Macrophages ◽  
Immunosuppressed Mice

Cynomorium songaricum Rupr. (CSP) have been used widely in TCM for many years, polysaccharides from CSP are main active component. In our previous research, we found that CSP play a role of immunomodulatory activity in vitro, but its mechanisms and in vivo immunomodulatory activity hadn’t been explored. In present study, we firstly extracted CSP and identified two new fractions CSP-a, CSP-b. To assess the immunomodulatory activity of CSP in vivo, cyclophosphamide (CTX)-induced immunosuppressed mice models were generated and then treated with CSP. The results demonstrated that CSP could improve thymus and spleen indices, phagocytic and clearance index, serum hemolysin, inflammatory cytokines productions in serum. To explore the mechanisms of CSP, CSP-a, CSP-b, RAW264.7 macrophages were used to evaluate the immunomodulatory activity in vitro, the results demonstrated that CSP, CSP-a, CSP-b can induce macrophage proliferation, enhance the phagocytic activity and increase cytokines expression. CSP, CSP-a, CSP-b possessed the immunomodulatory activity by inducing the phosphorylation of MAPKs. This study suggested that CSP may be useful for lessening chemotherapy-induced immunosuppression and proposed the basis for the clinical application of CSP.

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