Release of pro-inflammatory cytokines from muscle and bone causes tenocyte death in a novel rotator cuff in vitro explant culture model

Abstract Background: Glucocorticoids (GCs) injections are commonly used to relieve pain and improve function in patients with multiple shoulder disability, they cause detrimental effects on the rotator cuff tendons. Adipose stem cell-derived exosomes (ASC-Exos) reportedly recover impaired tendon matrix metabolism by maintaining tissue homeostasis. It is unclear whether additional ASC-Exos treatment overrides the detrimental effects of GCs without interfering with their anti-inflammatory effects.Methods: The in vitro studies included inflammatory analysis and cytoprotective analysis. In the inflammatory analysis, rat raw cells were treated with saline, GCs, or GCs + ASC-Exos and evaluated regarding cellular proliferation, migration, and secretion of inflammatory-related cytokines. In the cytoprotective analysis, rat tenocytes were treated with saline, GCs, or GCs + ASC-Exos and evaluated regarding cellular proliferation, migration, senescence, apoptosis, and transcription of tenocytic genes. In the in vivo studies, a subacromial injection of saline, GCs, or GCs + ASC-Exos was performed in a chronic injured-intact rotator cuff rat model. Histological and biomechanical analysis were performed 1 week to evaluate the protective effect of ASC-Exos against GCs-induced detriments on injured-intact in rotator cuffs.Results: In the in vitro inflammatory analysis, GCs treatment significantly decreased the proliferation, migration, and secretion of pro-inflammatory cytokines in raw cells, and increased the secretion of anti-inflammatory cytokines; additional ASC-Exos treatment further significantly decreased the secretion of pro-inflammatory cytokines and increased the secretion of anti-inflammatory cytokines, while restoring GCs-suppressed cellular proliferation and migration. In the in vitro cytoprotective analysis, GCs treatment significantly decreased the proliferation, migration, and transcription of tenocytic matrix molecules of tenocytes, and significantly increased their senescence, apoptosis, and transcription of ROS and tenocytic degradative enzymes; additional ASC-Exos treatment significantly improved the GCs-suppressed cellular proliferation, migration, and transcription of tenocytic matrix molecules, transcription of tenocytic degradative enzyme inhibitors, and significantly decreased the GCs-induced cell senescence, apoptosis, and transcription of ROS and tenocytic degradative enzymes. In the in vivo studies, an additional ASC-Exos injection restored the impaired histological and biomechanical properties owing to GCs administration.Conclusion: ASC-Exos may exert a stronger anti-inflammatory effect in combination with GCs, and override their detrimental effects on the rotator cuff.

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Methylmercury-induced pro-inflammatory cytokines activation and its preventive strategy using anti-inflammation N-acetyl-l-cysteine: a mini-review

Reviews on Environmental Health ◽

10.1515/reveh-2020-0026 ◽

2020 ◽

Vol 35 (3) ◽

pp. 233-238

Author(s):

Muflihatul Muniroh

Keyword(s):

Inflammatory Cytokines ◽

Health Concern ◽

Brain Cells ◽

Preventive Strategy ◽

Hearing Impairments ◽

Sensory Disturbances ◽

Anti Inflammation ◽

Pro Inflammatory Cytokines

AbstractThe exposure of methylmercury (MeHg) has become a public health concern because of its neurotoxic effect. Various neurological symptoms were detected in Minamata disease patients, who got intoxicated by MeHg, including paresthesia, ataxia, gait disturbance, sensory disturbances, tremors, visual, and hearing impairments, indicating that MeHg could pass the blood-brain barrier (BBB) and cause impairment of neurons and other brain cells. Previous studies have reported some expected mechanisms of MeHg-induced neurotoxicity including the neuroinflammation pathway. It was characterized by the up-regulation of numerous pro-inflammatory cytokines expression. Therefore, the use of anti-inflammatories such as N-acetyl-l-cysteine (NAC) may act as a preventive compound to protect the brain from MeHg harmful effects. This mini-review will explain detailed information on MeHg-induced pro-inflammatory cytokines activation as well as possible preventive strategies using anti-inflammation NAC to protect brain cells, particularly in in vivo and in vitro studies.

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Cladribine inhibits secretion of pro-inflammatory cytokines and phagocytosis in human monocyte-derived M1 macrophages in-vitro

International Immunopharmacology ◽

10.1016/j.intimp.2020.107270 ◽

2021 ◽

Vol 91 ◽

pp. 107270

Author(s):

Caroline B.K. Mathiesen ◽

Asha M. Rudjord-Levann ◽

Monika Gad ◽

Jesper Larsen ◽

Finn Sellebjerg ◽

...

Keyword(s):

Inflammatory Cytokines ◽

Human Monocyte ◽

M1 Macrophages ◽

Pro Inflammatory Cytokines

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Silica nanoparticles induce NLRP3 inflammasome activation in human primary immune cells

Innate Immunity ◽

10.1177/1753425917738331 ◽

2017 ◽

Vol 23 (8) ◽

pp. 697-708 ◽

Cited By ~ 19

Author(s):

Diana M Gómez ◽

Silvio Urcuqui-Inchima ◽

Juan C Hernandez

Keyword(s):

Physicochemical Properties ◽

Silica Nanoparticles ◽

Inflammatory Cytokines ◽

Nlrp3 Inflammasome ◽

Deep Understanding ◽

Inflammasome Activation ◽

Dependent Manner ◽

Dose Dependent ◽

Pro Inflammatory Cytokines

In recent years, the potential use of silica nanoparticles (SiNPs) among different biomedical fields has grown. A deep understanding of the physicochemical properties of nanoparticles (NPs) and their regulation of specific biological responses is crucial for the successful application of NPs. Exposure to NP physicochemical properties (size, shape, porosity, etc.) could result in deleterious effects on cellular functions, including a pro-inflammatory response mediated via activation of the NLRP3 inflammasome. The aim of this study was to evaluate the potential in vitro immunomodulatory effect of 12-nm and 200-nm SiNPs on the expression of pro-inflammatory cytokines and NLRP3 inflammasome components in human primary neutrophils and PBMCs. This study demonstrates that regardless of the size of the nanoparticles, SiNPs induce the production of pro-inflammatory cytokines in a dose-dependent manner. Induced IL-1β production after exposure to SiNPs suggests the involvement of NLRP3 inflammasome components participation in this process. In conclusion, SiNPs induce the production of pro-inflammatory cytokines in a dose-dependent manner. Furthermore, our data suggest that the production and release of IL-1β possibly occurs through the formation of the NLRP3 inflammasome.

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The protective effects of carvacrol and thymol against paracetamol–induced toxicity on human hepatocellular carcinoma cell lines (HepG2)

Human & Experimental Toxicology ◽

10.1177/0960327115627688 ◽

2016 ◽

Vol 35 (12) ◽

pp. 1252-1263 ◽

Cited By ~ 23

Author(s):

SS Palabiyik ◽

E Karakus ◽

Z Halici ◽

E Cadirci ◽

Y Bayir ◽

...

Keyword(s):

Oxidative Stress ◽

Inflammatory Cytokines ◽

Hepg2 Cells ◽

Folk Medicine ◽

Hepatoprotective Activity ◽

High Dose ◽

Protective Effects ◽

And Oxidative Stress ◽

Pro Inflammatory Cytokines

Acetaminophen (APAP) overdose could induce liver damage and lead to acute liver failure. The treatment of APAP overdoses could be improved by new therapeutic strategies. Thymus spp., which has many beneficial effects and has been used in folk medicine, is one such potential strategy. In the present study, the hepatoprotective activity of the main constituents of Thymus spp., carvacrol and thymol, were evaluated in light of APAP-induced hepatotoxicity. We hoped to understand the hepatoprotective mechanism of these agents on the antioxidant system and pro-inflammatory cytokines in vitro. Dose-dependent effects of thymol and carvacrol (25, 50, and 100 µM) were tested on cultured HepG2 cells. N-Acetylcysteine (NAC) was tested as positive control. We showed that APAP inhibited HepG2 cell growth by inducing inflammation and oxidative stress. Incubating APAP-exposed HepG2 cells with carvacrol and thymol for 24 h ameliorated this inflammation and oxidative stress. We also evaluated alanine transaminase and lactate dehydrogenase levels of HepG2 cells. We found that thymol and carvacrol protected against APAP-induced toxicity in HepG2 cells by increasing antioxidant activity and reducing pro-inflammatory cytokines, such as tumor necrosis factor α and interleukin 1β. Taking together high-dose thymol and carvacrol treatment has an effect close to NAC treatment in APAP toxicity, but thymol has better treatment effect than carvacrol.

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EFFECT OF EXOPOLISACCHARIDES OF LACTIC ACID BACTERIA ON THE SYNTHESIS OF PROINFLAMMATORY CYTOKINES BY MACROPHAGIC MICE IN PHAGOCYTOSIS OF STAPHYLOCOCCUS AUREUS

Journal of microbiology epidemiology immunobiology ◽

10.36233/0372-9311-2018-1-67-71 ◽

2018 ◽

pp. 67-71

Author(s):

G. T. Uryadova ◽

E. A. Gorelnikova ◽

N. A. Fokina ◽

A. S. Dolmashkina ◽

L. V. Karpunina

Keyword(s):

Staphylococcus Aureus ◽

Lactic Acid ◽

Lactic Acid Bacteria ◽

Lactococcus Lactis ◽

Inflammatory Cytokines ◽

Proinflammatory Cytokines ◽

Streptococcus Thermophilus ◽

Ambiguous Effect ◽

Pro Inflammatory Cytokines

Aim. Study of the effect of exopolysaccharides (EPS) of lactic acid cocci on cytokine activity of macrophages of mice with phagocytosis in vitro Staphylococcus aureus 209-P. Materials and methods. The EPS of Streptococcus thermophilus and Lactococcus lactis B-1662 was used in the work. At 13, 5 and 7, AMP and PMP were isolated and the phagocytosis process was modeled in vitro. After 30 minutes, 1, 6 and 24 hours, the content of pro-inflammatory cytokines IL-1a and TNF-a was determined. Results. EPSs had an ambiguous effect on the production of cytokines. The greatest effect on the synthesis was provided by EPS of S. thermophilus. Conclusion. The results of the study allow us to talk about the possibility of using EPS of S. thermophilus as a preventive immunomodulator for correction of the cytokine status of animals.

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Macrophage-Biomimetic Porous Se@SiO2 Nanocomposites For “Dual Model” Immunotherapy Against Inflammatory Osteolysis

10.21203/rs.3.rs-885656/v1 ◽

2021 ◽

Author(s):

Cheng Ding ◽

Chuang Yang ◽

Tao Cheng ◽

Xingyan Wang ◽

Qiaojie Wang ◽

...

Keyword(s):

Inflammatory Cytokines ◽

Inflammatory Responses ◽

Total Joint Replacement ◽

Major Complication ◽

Dual Model ◽

Joint Replacement Surgery ◽

Pro Inflammatory Cytokines ◽

Macrophage Membrane

Abstract Background：Inflammatory osteolysis is a major complication of total joint replacement surgery that can cause prosthesis failure and necessitate revision surgery. Macrophages are key effector immune cells in inflammatory responses, but excessive M1-polarization of dysfunctional macrophages leads to the secretion of pro-inflammatory cytokines and severe loss of bone tissue. Here, we report the development of macrophage-biomimetic porous SiO2-coated ultrasmall Se particles (Porous Se@SiO2 nanospheres) for the management of inflammatory osteolysis. Results: Macrophage-membrane-coated porous Se@SiO2 nanospheres(M-Se@SiO2) can attenuate lipopolysaccharide (LPS)-induced inflammatory osteolysis by a dual-immunomodulatory effect. As macrophage membrane decoys, these nanoparticles reduce toxin levels and neutralize pro-inflammatory cytokines. Moreover, the release of Se can induce the polarization of macrophages toward the anti-inflammatory M2-phenotype. These effects are mediated via the inhibition of p65, p38, and extracellular signal-regulated kinase(ERK) signaling. Additionally, the immune environment created by M-Se@SiO2 reduces the inhibition of osteogenic differentiation caused by pro-inflammation cytokines, confirmed through in vitro and in vivo experiments.Conclusion: Our findings suggest that M-Se@SiO2 has an immunomodulatory role in LPS-induced inflammation and bone remodeling, which demonstrates that M-Se@SiO2 is a promising engineered nano-platform for the treatment of osteolysis arising after arthroplasty.

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Ex vivo and in vitro production of pro-inflammatory cytokines in Blau syndrome

Reumatismo ◽

10.4081/reumatismo.2014.772 ◽

2015 ◽

Vol 66 (4) ◽

pp. 277 ◽

Cited By ~ 3

Author(s):

P. Galozzi ◽

O. Negm ◽

E. Greco ◽

N. Alkhattabi ◽

A. Gava ◽

...

Keyword(s):

Inflammatory Cytokines ◽

Ex Vivo ◽

Blau Syndrome ◽

In Vitro Production ◽

Vitro Production ◽

Pro Inflammatory Cytokines

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Abstract 319: Small Molecule Gβγ Inhibition Attenuates Cardiac Fibroblast Inflammatory and Pro-Fibrotic Signaling

Circulation Research ◽

10.1161/res.115.suppl_1.319 ◽

2014 ◽

Vol 115 (suppl_1) ◽

Author(s):

Joshua G Travers ◽

Fadia A Kamal ◽

Michael S Burhans ◽

Burns C Blaxall

Keyword(s):

Myocardial Fibrosis ◽

Inflammatory Cytokines ◽

Small Molecule ◽

Therapeutic Potential ◽

Interstitial Fibrosis ◽

Pressure Overload ◽

Cardiac Fibroblast ◽

Ventricular Compliance ◽

Pro Inflammatory Cytokines

Heart failure (HF) is a devastating disease characterized by chamber remodeling, interstitial fibrosis and reduced ventricular compliance. Prolonged sympathetic overstimulation promotes excess signaling through G-protein Gβγ subunits and ultimately results in pathologic GRK2-mediated β-adrenergic receptor (β-AR) downregulation. We have recently demonstrated the therapeutic potential of the small molecule Gβγ-GRK2 inhibitor Gallein in limiting HF progression. Pathologic activation of the cardiac fibroblast (CF) induces the transition to a myofibroblast phenotype, which plays a fundamental role in myocardial fibrosis and remodeling. We hypothesized that Gβγ-GRK2 inhibition plays an important functional role in the CF to attenuate pathologic CF activation, inflammation and interstitial fibrosis. To explore the effect of Gβγ-GRK2 inhibition on inflammation and pro-fibrotic signaling, mice were subjected to 7 days of transverse aortic constriction, a pressure-overload model of HF. In addition to the attenuation in overall cardiac hypertrophy, animals treated with Gallein displayed reduced expression of pro-inflammatory cytokines, including macrophage inflammatory protein 1 alpha (MIP-1α) and MIP-1β, along with Interleukin-6, as assessed by qPCR. Gallein-treated animals also exhibited diminished pro-fibrotic signaling, as evidenced by a reduction in the expression of TGFβ, a major driver of myocardial fibrosis, and decreased expression of collagen. To recapitulate these findings in vitro, primary adult mouse ventricular fibroblasts were pathologically stimulated using Isoproterenol (ISO, β-AR agonist) or Angiotensin II and treated +/- Gallein for 24 hours. CFs treated with Gallein displayed an analogous reduction in the expression of these pro-inflammatory cytokines and collagen. In summary, these data suggest a potential therapeutic role for small molecule Gβγ-GRK2 inhibition in limiting pathologic myofibroblast activation, inflammation and interstitial fibrosis. We believe this fibroblast-targeted approach will lead to the refinement of existing targets and compounds, and possibly the generation of novel therapeutics for the treatment of HF.

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Artemisinin improves neurocognitive deficits associated with sepsis by activating the AMPK axis in the microglia.

10.21203/rs.2.17969/v2 ◽

2020 ◽

Author(s):

Shao-Peng Lin ◽

Jue-Xian Wei ◽

Shan Ye ◽

Jiasong Hu ◽

Jingyi Bu ◽

...

Keyword(s):

Cognitive Impairment ◽

Inflammatory Cytokines ◽

Nuclear Translocation ◽

Neuronal Damage ◽

Protective Mechanism ◽

Protective Effects ◽

Neurocognitive Deficits ◽

Anti Inflammatory ◽

Pro Inflammatory Cytokines

Abstract Background and purpose: Artemisinin has been in use as an anti-malarial drug for almost half a century in the world. There is growing evidence that artemisinin also possesses potent anti-inflammatory and immunoregulatory properties. However, the efficacy of artemisinin treatment in neurocognitive deficits associated with sepsis remains unknown. Here, we evaluate the possible protective effects and explore the underlying mechanism of artemisinin on cognitive impairment resulting from sepsis.Methods: Male C57BL/6 mice were pretreated with either vehicle or artemisinin, and then injected with LPS to establish an animal model of sepsis. The cognitive function was then assessed using the Morris water maze. Neuronal damage and neuroinflammation in the hippocampus were evaluated by immunohistochemical and ELISA analysis. Additionally, the protective mechanism of artemisinin was determined in vitro.Results: The results showed that artemisinin preconditioning attenuated LPS-induced cognitive impairment, neural damage, and microglial activation in the mouse brain. The in vitro experiment revealed that artemisinin could reduce the production of pro-inflammatory cytokines and suppress the microglial migration in the BV2 microglia cells. Meanwhile, western blot demonstrated that artemisinin suppressed nuclear translocation of nuclear factor kappa-B and the expression of pro-inflammatory cytokines (i.e. tumor necrosis factor alpha, interleukin-6) by activating adenosine monophosphate-activated protein kinaseα1 (AMPKα1) pathway. Furthermore, knock-down of AMPKα1 markedly abolished the anti-inflammatory effects of artemisinin.Conclusion: Artemisinin is a potential therapeutic agent for sepsis-associated neuroinflammation and cognitive impairment, and its effect was probably mediated by the activation of AMPKα1 signalling pathway in microglia.

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