Astrocyte-Conditioned Medium Protects Prefrontal Cortical Neurons from Glutamate-Induced Cell Death by Inhibiting TNF-α Expression

2019 ◽  
Vol 26 (1) ◽  
pp. 33-42
Author(s):  
Cai Song ◽  
Yih-Shyuan Wu ◽  
Zhi-You Yang ◽  
Allan V. Kalueff ◽  
Yin-Yin Tsao ◽  
...  
Keyword(s):  
Cell Death ◽  
Conditioned Medium ◽  
Cortical Neurons ◽  
Prefrontal Cortical ◽  
Tnf Α ◽  
Astrocyte Conditioned Medium

scholarly journals Verbascoside-Rich Abeliophyllum distichum Nakai Leaf Extracts Prevent LPS-Induced Preterm Birth Through Inhibiting the Expression of Proinflammatory Cytokines from Macrophages and the Cell Death of Trophoblasts Induced by TNF-α

Molecules ◽  
2020 ◽  
Vol 25 (19) ◽  
pp. 4579
Author(s):  
Ho Won Kim ◽  
A-Reum Yu ◽  
Minji Kang ◽  
Nak-Yun Sung ◽  
Byung Soo Lee ◽  
...  
Keyword(s):  
Cell Death ◽  
Preterm Birth ◽  
Conditioned Medium ◽  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Fetal Loss ◽  
Trophoblast Cell ◽  
Tnf Α ◽  
Abeliophyllum Distichum ◽  
Cell Conditioned Medium

Background: Preterm birth is a known leading cause of neonatal mortality and morbidity. The underlying causes of pregnancy-associated complications are numerous, but infection and inflammation are the essential high-risk factors. However, there are no safe and effective preventive drugs that can be applied to pregnant women. Objective: The objectives of the study were to investigate a natural product, Abeliophyllum distichum leaf (ADL) extract, to examine the possibility of preventing preterm birth caused by inflammation. Methods: We used a mouse preterm birth model by intraperitoneally injecting lipopolysaccharides (LPS). ELISA, Western blot, real-time PCR and immunofluorescence staining analyses were performed to confirm the anti-inflammatory efficacy and related mechanisms of the ADL extracts. Cytotoxicity and cell death were measured using Cell Counting Kit-8 (CCK-8) analysis and flow cytometer. Results: A daily administration of ADL extract significantly reduced preterm birth, fetal loss, and fetal growth restriction after an intraperitoneal injection of LPS in mice. The ADL extract prevented the LPS-induced expression of TNF-α in maternal serum and amniotic fluid and attenuated the LPS-induced upregulation of placental proinflammatory genes, including IL-1β, IL-6, IL-12p40, and TNF-α and the chemokine gene CXCL-1, CCL-2, CCL3, and CCL-4. LPS-treated THP-1 cell-conditioned medium accelerated trophoblast cell death, and TNF-α played an essential role in this effect. The ADL extract reduced LPS-treated THP-1 cell-conditioned medium-induced trophoblast cell death by inhibiting MAPKs and the NF-κB pathway in macrophages. ADL extract prevented exogenous TNF-α-induced increased trophoblast cell death and decreased cell viability. Conclusions: We have demonstrated that the inhibition of LPS-induced inflammation by ADL extract can prevent preterm birth, fetal loss, and fetal growth restriction.

scholarly journals Early macrophage infiltrates impair pancreatic cancer cell growth by TNF-α secretion

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Cansu Tekin ◽  
Hella L. Aberson ◽  
Maarten F. Bijlsma ◽  
C. Arnold Spek
Keyword(s):  
Cell Death ◽  
Conditioned Medium ◽  
Cell Lines ◽  
Annexin V ◽  
Therapeutic Benefit ◽  
Ductal Adenocarcinoma ◽  
Potential Candidate ◽  
Tnf Α ◽  
The Impact

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is a grim disease with high mortality rates. Increased macrophage influx in PDAC is a common hallmark and associated with poor prognosis. Macrophages have high cellular plasticity, which can differentiate into both anti- and pro-tumorigenic properties. Here, we investigated how naïve (M0) macrophages differ from other macrophages in their anti-tumorigenic activities. Methods In vitro BrdU proliferation and Annexin V cell death analyses were performed on PANC-1 and MIA PaCa-2 PDAC cell lines exposed to conditioned medium of different macrophage subsets. Macrophage secreted factors were measured by transcript analysis and ELISA. Therapeutic antibodies were used to functionally establish the impact of the identified cytokine on PDAC proliferation. Results Proliferation and cell death assays revealed that only M0 macrophages harbor anti-tumorigenic activities and that M1, M2, and TAMs do not. mRNA analysis and ELISA results suggested TNF-α as a potential candidate to mediate M0 macrophage induced cell death. To demonstrate the importance of TNF-α in M0 macrophage-induced cell death, PANC-1 and MIA PaCa-2 cell-lines were exposed to M0 macrophage conditioned medium in the presence of the TNF-α inhibitor Infliximab, which effectively diminished the anti-tumor activities of M0 macrophages. Conclusion Newly tumor-infiltrated naive M0 macrophages exert anti-tumorigenic activities via TNF-α secretion. Their subsequent differentiation into either M1, M2, or TAM subsets reduces TNF-α levels, thereby abolishing their cytotoxic activity on PDAC cells. These data suggest that reestablishing TNF-α secretion in differentiated macrophages might yield a therapeutic benefit.

scholarly journals Conditioned medium from human gingival mesenchymal stem cells protects motor-neuron-like NSC-34 cells against scratch-injury-induced cell death

2017 ◽  
Vol 30 (4) ◽  
pp. 383-394 ◽  
Author(s):  
Thangavelu Soundara Rajan ◽  
Francesca Diomede ◽  
Placido Bramanti ◽  
Oriana Trubiani ◽  
Emanuela Mazzon
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Cell Death ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Motor Neuron ◽  
Conditioned Medium ◽  
Caspase 3 ◽  
Tnf Α ◽  
Anti Inflammatory

Neuronal cell death is a normal process during central nervous system (CNS) development and is also involved in the death of motor neurons in diverse spinal motor neuron degenerative diseases. Here, we investigated the neuroprotective effect of secretory factors released from human gingival mesenchymal stem cells (hGMSCs) in mechanically injured murine motor-neuron-like NSC-34 cells. The cells were exposed to scratch injury and the markers for apoptosis and oxidative stress were examined. Immunocytochemistry results showed that proapoptotic markers cleaved caspase-3 and Bax were elevated while anti-apoptotic protein Bcl-2 was suppressed in scratch-injured NSC-34 cells. Oxidative stress markers SOD-1, inducible nitric oxide synthase (iNOS), Cox-2, and proinflammatory cytokine tumor necrosis factor alpha (TNF-α) were activated. Conditioned medium (CM) derived from hGMSCs (hGMSC-CM) significantly blocked the cell death by suppressing SOD-1, iNOS, TNF-α, cleaved caspase-3, and Bax. Bcl-2 and anti-inflammatory cytokine anti-interleukin 10 (IL-10) were increased in hGMSC-CM-treated injured cells. Moreover, hGMSC-CM treatment upregulated neurotrophins anti-brain-derived neurotrophic factor (BDNF) and NT3. Western blot data of hGMSC-CM revealed the presence of neurotrophins nerve growth factor (NGF), NT3, anti-inflammatory cytokines IL-10, and transforming growth factor beta (TGF-β), suggesting their positive role to elicit neuroprotection. Our results propose that hGMSC-CM may serve as a simple and potential autologous therapeutic tool to treat motor neuron injury.

scholarly journals Early macrophage infiltrates impair pancreatic cancer cell growth by TNF-α secretion

2020 ◽  
Author(s):  
Cansu Tekin ◽  
Hella L Aberson ◽  
Maarten F Bijlsma ◽  
C. Arnold Spek
Keyword(s):  
Cell Death ◽  
Conditioned Medium ◽  
Cell Lines ◽  
Annexin V ◽  
Therapeutic Benefit ◽  
Ductal Adenocarcinoma ◽  
Potential Candidate ◽  
Tnf Α ◽  
The Impact

Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) is a grim disease with high mortality rates. Increased macrophage influx in PDAC is a common hallmark and associated with poor prognosis. Macrophages have high cellular plasticity, which can differentiate into both anti- and pro-tumorigenic properties. Here, we investigated how naïve (M0) macrophages differ from other macrophages in their anti-tumorigenic activities.Methods: In vitro BrdU proliferation and Annexin V cell death analyses were performed on PANC-1 and MIA PaCa-2 PDAC cell lines exposed to conditioned medium of different macrophage subsets. Macrophage secreted factors were measured by transcript analysis and ELISA. Therapeutic antibodies were used to functionally establish the impact of the identified cytokine on PDAC proliferation.Results: Proliferation and cell death assays revealed that only M0 macrophages harbor anti-tumorigenic activities and that M1, M2, and TAMs do not. mRNA analysis and ELISA results suggested TNF-α as a potential candidate to mediate M macrophage induced cell death. To demonstrate the importance of TNF-α in M macrophage-induced cell death, PANC-1 and MIA PaCa-2 cell-lines were exposed to M macrophage conditioned medium in the presence of the TNF-α inhibitor Infliximab, which effectively diminished the anti-tumor activities of M0 macrophages.Conclusion: Newly tumor-infiltrated naive M0 macrophages exert anti-tumorigenic activities via TNF-α secretion. Their subsequent differentiation into either M1, M2, or TAM subsets reduces TNF-α levels, thereby abolishing their cytotoxic activity on PDAC cells. These data suggest that reestablishing TNF-α secretion in differentiated macrophages might yield a therapeutic benefit.

Sign in / Sign up

Export Citation Format

Share Document