Neonatal rat microglia derived from different brain regions have distinct activation responses

The regional heterogeneity of neuronal phenotypes is a well-known phenomenon. Whether or not glia derived from different brain regions are phenotypically and functionally distinct is less clear. Here, we show that microglia, the resident immune cells of the brain, display region-specific responses for activating agents including glutamate (GLU), lipopolysaccharide (LPS) and adenosine 5′-triphosphate (ATP). Primary microglial cultures were prepared from brainstem (Brs), cortex (Ctx), hippocampus (Hip), striatum (Str) and thalamus (Thl) of 1-day-old rats and were shown to upregulate the release of nitric oxide (NO) and brain-derived neurotrophic factor (BDNF) in a region- and activator-specific manner. With respect to ATP specifically, ATP-induced changes in microglial tumor necrosis factor-α (TNF-α) release, GLU uptake and purinergic receptor expression were also regionally different. When co-cultured with hypoxia (Hyp)-injured neurons, ATP-stimulated microglia from different regions induced different levels of neurotoxicity. These region-specific responses could be altered by pre-conditioning the microglia in a different neurochemical milieu, with taurine (TAU) being one of the key molecules involved. Together, our results demonstrate that microglia display a regional heterogeneity when activated, and this heterogeneity likely arises from differences in the environment surrounding the microglia. These findings present an additional mechanism that may help to explain the regional selectiveness of various brain pathologies.

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Effects of Polyphenolic Compounds on Tumor Necrosis Factor-α (TNF-α)-Induced Changes of Adipokines and Oxidative Stress in 3T3-L1 Adipocytes

Journal of Agricultural and Food Chemistry ◽

10.1021/jf1036992 ◽

2011 ◽

Vol 59 (2) ◽

pp. 546-551 ◽

Cited By ~ 50

Author(s):

Gow-Chin Yen ◽

Yi-Chen Chen ◽

Wei-Tang Chang ◽

Chin-Lin Hsu

Keyword(s):

Oxidative Stress ◽

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Polyphenolic Compounds ◽

Tnf Α ◽

Factor Α ◽

Induced Changes ◽

And Oxidative Stress ◽

Necrosis Factor

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The effects of chronic exercise on the inflammatory cytokines interleukin-6 and tumor necrosis factor-α are different with age

Applied Physiology Nutrition and Metabolism ◽

10.1139/h2012-039 ◽

2012 ◽

Vol 37 (4) ◽

pp. 631-636 ◽

Cited By ~ 11

Author(s):

Min Kyong Moon ◽

Bong Jun Cho ◽

You Jin Lee ◽

Sung Hee Choi ◽

Soo Lim ◽

...

Keyword(s):

Tumor Necrosis Factor ◽

Endurance Exercise ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Young Rats ◽

Tnf Α ◽

Cytokine Levels ◽

Old Rats ◽

Factor Α ◽

Necrosis Factor

Aging is associated with chronic low-grade inflammation, and interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) are key mediators of the inflammatory process. IL-6, especially muscle-derived IL-6, is expected to mediate the beneficial metabolic effects of exercise. There was no report that directly compares the effects of chronic endurance exercise on cytokine responses between old and young subjects in the same situation. Therefore, we compared the effects of endurance exercise on the expression of IL-6 and TNF-α in old and young rats. Young (3-month-old) and old (20-month-old) male Fisher rats were trained for 12 weeks on the treadmill. We measured serum TNF-α and IL-6 concentrations by enzyme-linked immunosorbent assay and examined mRNA expression of TNF-α and IL-6 in muscle, liver, and white adipose tissue using reverse transcription – polymerase chain reaction. We found that old rats had higher basal IL-6 levels in the liver, as well as in the serum and the muscle. After chronic endurance exercise, young rats exhibited significant decreases in serum TNF-α levels and hepatic IL-6 expression. However, old rats exhibited no significant changes in either serum or tissue cytokine levels after endurance exercise. These findings suggest that chronic endurance exercise could influence the inflammatory response of hepatic tissues, as well as muscle, and that the effects of chronic endurance exercise on inflammatory cytokine levels are different between old and young rats and an exercise program tailored for old subjects will be needed to obtain beneficial anti-inflammatory effects from exercise.

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Endothelial permeability and IL-6 production during hypoxia: role of ROS in signal transduction

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1999.277.5.l1057 ◽

1999 ◽

Vol 277 (5) ◽

pp. L1057-L1065 ◽

Cited By ~ 40

Author(s):

Mir H. Ali ◽

Scott A. Schlidt ◽

Navdeep S. Chandel ◽

Karen L. Hynes ◽

Paul T. Schumacker ◽

...

Keyword(s):

Cytokine Production ◽

Umbilical Vein ◽

Endothelial Permeability ◽

Ros Generation ◽

Transendothelial Electrical Resistance ◽

Tnf Α ◽

Factor Α ◽

Induced Changes ◽

Necrosis Factor

Prolonged hypoxia produces reversible changes in endothelial permeability, but the mechanisms involved are not fully known. Previous studies have implicated reactive oxygen species (ROS) and cytokines in the regulation of permeability. We tested whether prolonged hypoxia alters permeability to increasing ROS generation, which amplifies cytokine production. Human umbilical vein endothelial cell (HUVEC) monolayers were exposed to hypoxia while secretion of tumor necrosis factor-α (TNF-α), interleukin (IL)-1α, IL-6, and IL-8 was measured. IL-6 and IL-8 secretion increased fourfold over 24 h in a pattern corresponding to changes in HUVEC permeability measured by transendothelial electrical resistance (TEER). Addition of exogenous IL-6 to normoxic HUVEC monolayers caused time-dependent changes in TEER that mimicked the hypoxic response. An antibody to IL-6 significantly attenuated the hypoxia-induced changes in TEER (86 ± 4 vs. 63 ± 3% with hypoxia alone at 18 h), whereas treatment with anti-IL-8 had no effect. To determine the role of hypoxia-induced ROS on this response, HUVEC monolayers were incubated with the antioxidants ebselen (50 μM) and N-acetyl-l-cysteine (NAC, 1 mM) before hypoxia. Antioxidants attenuated hypoxia-induced IL-6 secretion (13 ± 2 pg/ml with ebselen and 19 ± 3 pg/ml with NAC vs. 140 ± 15 pg/ml with hypoxia). Ebselen and NAC prevented changes in TEER during hypoxia (94 ± 2% with ebselen and 90 ± 6% with NAC vs. 63 ± 3% with hypoxia at 18 h). N-nitro-l-arginine (500 μM) did not decrease hypoxia-induced changes in dichlorofluorescin fluorescence, IL-6 secretion, or TEER. Thus ROS generated during hypoxia act as signaling elements, regulating secretion of the proinflammatory cytokines that lead to alterations of endothelial permeability.

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Tumor necrosis factor-α alters integrins and metalloprotease ADAM12 levels and signaling in differentiating myoblasts

Polish Journal of Veterinary Sciences ◽

10.1515/pjvs-2016-0032 ◽

2016 ◽

Vol 19 (2) ◽

pp. 253-259

Author(s):

K. Grzelkowska-Kowalczyk ◽

J. Tokarska ◽

K. Grabiec ◽

M. Gajewska ◽

M. Milewska ◽

...

Keyword(s):

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Integrin Receptors ◽

Integrin Β1 ◽

Tnf Α ◽

Integrin Α5 ◽

Factor Α ◽

Induced Changes ◽

Necrosis Factor

AbstractThe extracellular matrix (ECM) is important in the regulation of myogenesis. We hypothesized that tumor necrosis factor-α (TNF-α) modifies ECM during differentiation of mouse C2C12 myoblasts. Exogenous TNF-α (1 ng/ml) stimulated myoblast fusion on the 3rdday (by 160% vs control) but not on the 5thday of myogenesis. The level of integrin α5 was significantly augmented by TNF-α during 5 day-differentiation; however, integrin β1 was higher than control only on the 3rdday of cytokine treatment. Both the abundance of integrin α5 bound to actin and the level of integrin β1 complexed with integrin α5 increased in the presence of TNF-α, especially on the 3rdday of differentiation. Similarly, the stimulatory effects of TNF-α on integrin α3, metalloprotease ADAM12 and kinases related to integrins, FAK and ILK, were limited to the 3rdday of differentiation. We concluded that TNF-α-induced changes in ECM components in differentiating myogenic cells, i.e. i) increased expression of integrin α5, β1, α3, and metalloprotease ADAM12, ii) enhanced formation of α5β1 integrin receptors and interaction of integrin α5-cytoskeleton, and iii) increased expression of kinases associated with integrin signaling, FAK and ILK, were temporarily associated with the onset of myocyte fusion.

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Anti-Inflammatory Effect of Simonsinol on Lipopolysaccharide Stimulated RAW264.7 Cells through Inactivation of NF-κB Signaling Pathway

Molecules ◽

10.3390/molecules25163573 ◽

2020 ◽

Vol 25 (16) ◽

pp. 3573

Author(s):

Lian-Chun Li ◽

Zheng-Hong Pan ◽

De-Sheng Ning ◽

Yu-Xia Fu

Keyword(s):

Nitric Oxide ◽

Signaling Pathway ◽

Morphological Changes ◽

Raw264.7 Cells ◽

Enzyme Linked Immunosorbent Assay ◽

Tnf Α ◽

Anti Inflammatory ◽

Factor Α ◽

Oxide Synthase ◽

Necrosis Factor

Simonsinol is a natural sesqui-neolignan firstly isolated from the bark of Illicium simonsii. In this study, the anti-inflammatory activity of simonsinol was investigated with a lipopolysaccharide (LPS)-stimulated murine macrophages RAW264.7 cells model. The results demonstrated that simonsinol could antagonize the effect of LPS on morphological changes of RAW264.7 cells, and decrease the production of nitric oxide (NO), tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6) in LPS-stimulated RAW264.7 cells, as determined by Griess assay and enzyme-linked immunosorbent assay (ELISA). Furthermore, simonsinol could downregulate transcription of inducible nitric oxide synthase (iNOS), TNF-α, and IL-6 as measured by reverse transcription polymerase chain reaction (RT-PCR), and inhibit phosphorylation of the alpha inhibitor of NF-κB (IκBα) as assayed by Western blot. In conclusion, these data demonstrate that simonsinol could inhibit inflammation response in LPS-stimulated RAW264.7 cells through the inactivation of the nuclear transcription factor kappa-B (NF-κB) signaling pathway.

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#50 Gestational exposure of tumor necrosis factor-α (TNF-α) inhibitor drugs

Reproductive Toxicology ◽

10.1016/j.reprotox.2019.05.068 ◽

2019 ◽

Vol 88 ◽

pp. 149-150 ◽

Cited By ~ 1

Author(s):

Erkoseoglu Ilknur ◽

Kadioglu Mine ◽

Cavusoglu Irem ◽

Sisman Mulkiye ◽

Aran Turhan ◽

...

Keyword(s):

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Gestational Exposure ◽

Tnf Α ◽

Factor Α ◽

Necrosis Factor

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Tumor Necrosis Factor-α Production-Enhancing Properties of Novel Adamantylalkylthio Derivatives of Some Heterocyclic Compounds

Zeitschrift für Naturforschung B ◽

10.1515/znb-2005-0419 ◽

2005 ◽

Vol 60 (4) ◽

pp. 471-475 ◽

Cited By ~ 2

Author(s):

Barbara Orzeszko ◽

Tomasz Świtaj ◽

Anna B. Jakubowska-Mućka ◽

Witold Lasek ◽

Andrzej Orzeszko ◽

...

Keyword(s):

Tumor Necrosis Factor ◽

Heterocyclic Compounds ◽

Tumor Necrosis ◽

The Novel ◽

Necrosis Factor Alpha ◽

Tnf Α ◽

Factor Alpha ◽

Factor Α ◽

Derivatives Of ◽

Necrosis Factor

Certain adamantylated heterocycles were previously shown to enhance the secretion of tumor necrosis factor alpha (TNF-α) by murine melanoma cells that have been transduced with the gene for human TNF-α and constitutively expressed this cytokine. The stimulatory potency of those compounds depended, among other factors, on the structure of the linker between the adamantyl residue and the heterocyclic core. In the present study, a series of (1-adamantyl)alkylsulfanyl derivatives of heterocyclic compounds was prepared by alkylation of the corresponding thioheterocyles. Of the novel adamantylalkylthio compounds tested in the aforementioned cell line, 2-(2-adamantan-1-ylethylsulfanyl)- 4-methyl-pyrimidine was found to be the most active

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Tumor necrosis factor α Inhibition for Alzheimer’s Disease

Journal of Central Nervous System Disease ◽

10.1177/1179573517709278 ◽

2017 ◽

Vol 9 ◽

pp. 117957351770927 ◽

Cited By ~ 43

Author(s):

Rudy Chang ◽

Kei-Lwun Yee ◽

Rachita K Sumbria

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Short Review ◽

Tnf Α ◽

Factor Α ◽

Ad Therapy ◽

Necrosis Factor

Tumor necrosis factor α (TNF-α) plays a central role in the pathophysiology of Alzheimer’s disease (AD). Food and Drug Administration–approved biologic TNF-α inhibitors are thus a potential treatment for AD, but they do not cross the blood-brain barrier. In this short review, we discuss the involvement of TNF-α in AD, challenges associated with the development of existing biologic TNF-α inhibitors for AD, and potential therapeutic strategies for targeting TNF-α for AD therapy.

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Tumor necrosis factor-α-associated lysosomal permeabilization is cathepsin B dependent

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00151.2002 ◽

2002 ◽

Vol 283 (4) ◽

pp. G947-G956 ◽

Cited By ~ 113

Author(s):

Nathan W. Werneburg ◽

M. Eugenia Guicciardi ◽

Steven F. Bronk ◽

Gregory J. Gores

Keyword(s):

Tumor Necrosis Factor ◽

Cathepsin B ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Fluorescent Protein ◽

Tnf Α ◽

Calcein Release ◽

Green Fluorescent ◽

Factor Α ◽

Necrosis Factor

Cathepsin B (Cat B) is released from lysososomes during tumor necrosis factor-α (TNF-α) cytotoxic signaling in hepatocytes and contributes to cell death. Sphingosine has recently been implicated in lysosomal permeabilization and is increased in the liver by TNF-α. Thus the aims of this study were to examine the mechanisms involved in TNF-α-associated lysosomal permeabilization, especially the role of sphingosine. Confocal microscopy demonstrated Cat B-green fluorescent protein and LysoTracker Red were both released from lysosomes after treatment of McNtcp.24 cells with TNF-α/actinomycin D, a finding compatible with lysosomal destabilization. In contrast, endosomes labeled with Texas Red dextran remained intact, suggesting lysosomes were specifically targeted for permeabilization. LysoTracker Red was released from lysosomes in hepatocytes treated with TNF-α or sphingosine in Cat B(+/+) but not Cat B(−/−) hepatocytes, as assessed by a fluorescence-based assay. With the use of a calcein release assay in isolated lysosomes, sphingosine permeabilized liver lysosomes isolated from Cat B(+/+) but not Cat B(−/−) liver. C6ceramide did not permeabilize lysosomes. In conclusion, these data implicate a sphingosine-Cat B interaction inducing lysosomal destabilization during TNF-α cytotoxic signaling.

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