TNF-α Induces MMP2 Gelatinase Activity and MT1-MMP Expression in an In Vitro Model of Nucleus Pulposus Tissue Degeneration

Spine ◽  
2008 ◽  
Vol 33 (4) ◽  
pp. 356-365 ◽  
Author(s):  
Cheryle A. Séguin ◽  
Robert M. Pilliar ◽  
Joseph A. Madri ◽  
Rita A. Kandel
Keyword(s):  
Nucleus Pulposus ◽  
In Vitro Model ◽  
Gelatinase Activity ◽  
Nucleus Pulposus Tissue ◽  
Tissue Degeneration ◽  
Tnf Α ◽  
Vitro Model

Induction of osteoclastogenesis in an in vitro model of Gaucher disease is mediated by T cells via TNF-α

Gene ◽  
2012 ◽  
Vol 509 (1) ◽  
pp. 51-59 ◽  
Author(s):  
Juan M. Mucci ◽  
Romina Scian ◽  
Pablo N. De Francesco ◽  
Florencia Suqueli García ◽  
Romina Ceci ◽  
...  
Keyword(s):  
T Cells ◽  
Gaucher Disease ◽  
In Vitro Model ◽  
Tnf Α ◽  
Vitro Model

scholarly journals Aβ oligomers trigger necroptosis-mediated neurodegeneration via microglia activation in Alzheimer′s disease.

2021 ◽  
Author(s):  
Natalia Salvadores ◽  
Ines Moreno ◽  
Nazareth Gamez ◽  
Gabriel Quiroz ◽  
Laura Vegas ◽  
...  
Keyword(s):  
Microglial Activation ◽  
In Vitro Model ◽  
Amyloid Β ◽  
Etiologic Agent ◽  
Neuron Death ◽  
Aβ Oligomers ◽  
Therapeutic Implications ◽  
Tnf Α ◽  
Vitro Model

Alzheimer′s disease (AD) is a major adult-onset neurodegenerative condition with no available treatment. Compelling reports point amyloid-β (Aβ) as the main etiologic agent that triggers AD. Although there is extensive evidence of a detrimental crosstalk between Aβ and microglia that contributes to neuroinflammation in AD, the exact mechanism leading to neuron death remains unknown. Using postmortem human AD brain tissue, we show that Aβ oligomers (Aβo) colocalize with the necroptosis effector pMLKL. Moreover, we found that the burden of Aβo correlates with the expression of key markers of necroptosis activation. Additionally, inhibition of necroptosis by pharmacological or genetic means, reduce neurodegeneration and memory impairment triggered by Aβo in mice. Since microglial activation is emerging as a central driver for AD pathogenesis, we then tested the contribution of microglia to the mechanism of Aβo-mediated necroptosis activation in neurons. Using an in vitro model, we show that conditioned medium from Aβo-stimulated microglia elicited necroptosis in neurons through activation of TNF-α signaling, triggering extensive neurodegeneration. Notably, necroptosis inhibition provided significant neuronal protection. Together, these findings suggest that Aβo-mediated microglia stimulation in AD contributes to necroptosis activation in neurons and neurodegeneration. As necroptosis is a druggable degenerative mechanism, our findings might have important therapeutic implications to prevent the progression of AD.

GSK-3 mediates differentiation and activation of proinflammatory dendritic cells

Blood ◽  
2006 ◽  
Vol 109 (4) ◽  
pp. 1584-1592 ◽  
Author(s):  
Elena Rodionova ◽  
Michael Conzelmann ◽  
Eugene Maraskovsky ◽  
Michael Hess ◽  
Michael Kirsch ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
In Vitro Model ◽  
Glycogen Synthase ◽  
Human Monocyte ◽  
Glycogen Synthase Kinase 3 ◽  
Inhibitory Effects ◽  
Tnf Α ◽  
Vitro Model

Abstract The key components of the intracellular molecular network required for the expression of a specific function of dendritic cells (DCs) are as yet undefined. Using an in vitro model of human monocyte-derived DC differentiation, this study investigates the role of glycogen synthase kinase 3 (GSK-3), a multifunctional enzyme critical for cellular differentiation, apoptosis, self-renewal, and motility, in this context. We demonstrate that GSK-3 (1) inhibits macrophage development during differentiation of DCs, (2) is constitutively active in immature DCs and suppresses spontaneous maturation, and (3) acquires a proinflammatory functional status mediating high levels of IL-12, IL-6, and TNF-α secretion, and partially inhibits IL-10 in the context of DC activation. In particular, GSK-3 enhances IL-12p35 mRNA expression and thus the production of the proinflammatory cytokine IL-12p70 by integrating the activities of other kinases priming GSK-3 targets and the inhibitory effects of Akt-1. GSK-3 may therefore act as a key integrator of activating and inhibitory pathways involved in proinflammatory DC differentiation and activation.

Interleukin-8 stimulates the migration of human colonic epithelial cells in vitro

1999 ◽  
Vol 97 (3) ◽  
pp. 385-390 ◽  
Author(s):  
Andrew J. WILSON ◽  
Keith BYRON ◽  
Peter R. GIBSON
Keyword(s):  
Cell Migration ◽  
Epithelial Cells ◽  
In Vitro Model ◽  
Interleukin 8 ◽  
Colonic Epithelium ◽  
Dependent Manner ◽  
Colonic Epithelial Cells ◽  
Tnf Α ◽  
Vitro Model

The migration of colonic epithelial cells (restitution) is an important event in the repair of mucosal injuries. Interleukin-8 (IL-8) is a physiological initiator of the chemotactic migration of leucocytes. This study aimed to determine whether IL-8 had a similar effect on migration in an in vitro model of wounded colonic epithelium. Cell migration over 24 h was assessed in circular wounds made in confluent monolayers of the human colon cancer cell line LIM1215. This migration was stimulated in a concentration-dependent manner by IL-8, with maximal effects of approx. 1.75-fold above basal migration. The motogenic effect of IL-8 was mediated independently of effects on cell proliferation. In contrast, it was partially dependent upon gene transcription and protein synthesis and involved the activation of pertussis-toxin-sensitive G-proteins. The short-chain fatty acids, acetate, propionate, butyrate and valerate, the activator of protein kinase C (phorbol-12-myristate-13-acetate) and tumour necrosis factor-α (TNF-α) all stimulated the secretion of IL-8. However, only the motogenic effect of TNF-α was dependent upon IL-8. In conclusion, IL-8 stimulated cell migration in an in vitro model of colonic epithelium, whereas the motogenic effect of at least one physiologically relevant factor was dependent upon an increase in its endogenous levels. If IL-8 stimulates colonic epithelial restitution in vivo, this would have ramifications for the control of repair processes following wounding of the colonic mucosa.

scholarly journals Modulation of Adhesion Process, E-Selectin and VEGF Production by Anthocyanins and Their Metabolites in an In Vitro Model of Atherosclerosis

Nutrients ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 655 ◽  
Author(s):  
Mirko Marino ◽  
Cristian Del Bo’ ◽  
Massimiliano Tucci ◽  
Dorothy Klimis-Zacas ◽  
Patrizia Riso ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
In Vitro Model ◽  
Vascular Endothelial ◽  
Tnf Α ◽  
Vitro Model ◽  
Factor Α ◽  
Endothelial Growth Factor ◽  
Adhesion Process ◽  
Necrosis Factor

The present study aims to evaluate the ability of peonidin and petunidin-3-glucoside (Peo-3-glc and Pet-3-glc) and their metabolites (vanillic acid; VA and methyl-gallic acid; MetGA), to prevent monocyte (THP-1) adhesion to endothelial cells (HUVECs), and to reduce the production of vascular cell adhesion molecule (VCAM)-1, E-selectin and vascular endothelial growth factor (VEGF) in a stimulated pro-inflammatory environment, a pivotal step of atherogenesis. Tumor necrosis factor-α (TNF-α; 100 ng mL−1) was used to stimulate the adhesion of labelled monocytes (THP-1) to endothelial cells (HUVECs). Successively, different concentrations of Peo-3-glc and Pet-3-glc (0.02 µM, 0.2 µM, 2 µM and 20 µM), VA and MetGA (0.05 µM, 0.5 µM, 5 µM and 50 µM) were tested. After 24 h, VCAM-1, E-selectin and VEGF were quantified by ELISA, while the adhesion process was measured spectrophotometrically. Peo-3-glc and Pet-3-glc (from 0.02 µM to 20 µM) significantly (p < 0.0001) decreased THP-1 adhesion to HUVECs at all concentrations (−37%, −24%, −30% and −47% for Peo-3-glc; −37%, −33%, −33% and −45% for Pet-3-glc). VA, but not MetGA, reduced the adhesion process at 50 µM (−21%; p < 0.001). At the same concentrations, a significant (p < 0.0001) reduction of E-selectin, but not VCAM-1, was documented. In addition, anthocyanins and their metabolites significantly decreased (p < 0.001) VEGF production. The present findings suggest that while Peo-3-glc and Pet-3-glc (but not their metabolites) reduced monocyte adhesion to endothelial cells through suppression of E-selectin production, VEGF production was reduced by both anthocyanins and their metabolites, suggesting a role in the regulation of angiogenesis.

scholarly journals Differences in statin associated neuroprotection corresponds with either decreased production of IL-1β or TNF-α in an in vitro model of neuroinflammation-induced neurodegeneration

2018 ◽  
Vol 344 ◽  
pp. 56-73 ◽  
Author(s):  
A.J. McFarland ◽  
A.K. Davey ◽  
C.M. McDermott ◽  
G.D. Grant ◽  
J. Lewohl ◽  
...  
Keyword(s):  
In Vitro Model ◽  
Tnf Α ◽  
Vitro Model

Lactobacillus delbrueckii subsp lactis CIDCA 133 modulates response of human epithelial and dendritic cells infected with Bacillus cereus.

2016 ◽  
Vol 7 (5) ◽  
pp. 749-760 ◽  
Author(s):  
I.S. Rolny ◽  
I. Tiscornia ◽  
S.M. Racedo ◽  
P.F. Pérez ◽  
M. Bollati-Fogolín
Keyword(s):  
Dendritic Cells ◽  
Bacillus Cereus ◽  
In Vitro Model ◽  
Probiotic Strain ◽  
Lactobacillus Delbrueckii ◽  
Tnf Α ◽  
Vitro Model ◽  
Ht 29 ◽  
Lactobacillus Delbrueckii Subsp

It is known that probiotic microorganisms are able to modulate pathogen virulence. This ability is strain dependent and involves multiple interactions between microorganisms and relevant host’s cell populations. In the present work we focus on the effect of a potentially probiotic lactobacillus strain (Lactobacillus delbrueckii subsp. lactis CIDCA 133) in an in vitro model of Bacillus cereus infection. Our results showed that infection of intestinal epithelial HT-29 cells by B. cereus induces nuclear factor kappa B (NF-κB) pathway. Noteworthy, the presence of strain L. delbrueckii subsp.lactis CIDCA 133 increases stimulation. However, B. cereus-induced interleukin (IL)-8 production by epithelial cells is partially abrogated by L. delbrueckii subsp. lactis CIDCA 133. These findings suggest that signalling pathways other than that of NF-κB are involved. In a co-culture system (HT-29 and monocyte-derived dendritic cells), B. cereus was able to translocate from the epithelial (upper) to the dendritic cell compartment (lower). This translocation was partially abrogated by the presence of lactobacilli in the upper compartment. In addition, infection of epithelial cells in the co-culture model, led to an increase in the expression of CD86 by dendritic cells. This effect could not be modified in the presence of lactobacilli. Interestingly, infection of enterocytes with B. cereus triggers production of proinflammatory cytokines by dendritic cells (IL-8, IL-6 and tumour necrosis factor alpha (TNF-α)). The production of TNF-α (a protective cytokine in B. cereus infections) by dendritic cells was increased in the presence of lactobacilli. The present work demonstrates for the first time the effect of L. delbrueckii subsp. lactis CIDCA 133, a potentially probiotic strain, in an in vitro model of B. cereus infection. The presence of the probiotic strain modulates cell response both in infected epithelial and dendritic cells thus suggesting a possible beneficial effect of selected lactobacilli strains on the course of B. cereus infection.

scholarly journals Anti-inflammatory Effects of Alcohol Are Associated with JNK-STAT3 Downregulation in an In Vitro Inflammation Model in HepG2 Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Katharina Mörs ◽  
Ramona Sturm ◽  
Jason-Alexander Hörauf ◽  
Shinwan Kany ◽  
Paola Cavalli ◽  
...  
Keyword(s):  
Hepg2 Cells ◽  
Acute Inflammation ◽  
In Vitro Model ◽  
Prolonged Exposure ◽  
Acute Exposure ◽  
High Dose ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Vitro Model

Background. In several preclinical and in vitro models of acute inflammation, alcohol (ethanol, EtOH) has been described as an immunomodulatory agent. Similarly, in different pathologies, clinical observations have confirmed either pro- or anti-inflammatory effects of EtOH. The liver plays an important role in immunity and alcohol metabolism; therefore, we analysed dose- and time-dependent effects of EtOH on the inflammatory response of human liver cells in an in vitro model of acute inflammation. Methods. HepG2 cells were stimulated with IL-1β and subsequently exposed to EtOH in a low or high dose (85 mM, LoD or 170 mM, HiD) for 1 h (acute exposure) or 72 h (prolonged exposure). IL-6 and TNF-α release was determined by ELISA. Cell viability, adhesion of isolated neutrophils to HepG2 monolayers, their ICAM-1 expression, and the activation of stress-induced protein kinase/c-Jun N-terminal kinase (SAPK/JNK) or signal transducer and activator of transcription 3 (STAT3) were analysed. Results. In this experimental design, EtOH did not markedly change the cell viability. Acute and prolonged exposure to EtOH significantly reduced dose-independent IL-1β-induced IL-6 and TNF-α release, as well as adhesion capacity to pretreated HepG2 cells. Acute exposure to EtOH significantly decreased the percentage of ICAM-1-expressing cells. IL-1β stimulation notably increased the activation of SAPK/JNK. However, low-dose EtOH exposure reduced this activation considerably, in contradiction to high-dose EtOH exposure. Acute exposure to LoD EtOH significantly diminished the IL-1β-induced STAT3 activation, whereas an acute exposure of cells to either HiD EtOH or in a prolonged setting showed no effects on STAT3 activation. Conclusion. EtOH exerts anti-inflammatory potential in this in vitro model of hepatic inflammation. These effects are associated with the reduced activation of JNK/STAT3 by EtOH, particularly in the condition of acute exposure to low-dose EtOH.

scholarly journals Dimethylfumarate inhibits microglial and astrocytic inflammation by suppressing the synthesis of nitric oxide, IL-1β, TNF-α and IL-6 in an in-vitro model of brain inflammation

2010 ◽  
Vol 7 (1) ◽  
pp. 30 ◽  
Author(s):  
Henrik Wilms ◽  
Jobst Sievers ◽  
Uta Rickert ◽  
Martin Rostami-Yazdi ◽  
Ulrich Mrowietz ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
In Vitro Model ◽  
Brain Inflammation ◽  
Tnf Α ◽  
Vitro Model
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