Cadmium-induced IL-6 and IL-8 expression and release from astrocytes are mediated by MAPK and NF-κB pathways

Phuagkhaopong, Suttinee; Ospondpant, Dusadee; Kasemsuk, Thitima; Sibmooh, Nathawut; Soodvilai, Sunhapas; Power, Christopher; Vivithanaporn, Pornpun

doi:10.1016/j.neuro.2017.03.001

Cited by 99 publications

(51 citation statements)

References 51 publications

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“…In the present study, we demonstrated that after infrasound exposure, astrocyte activation was significant and the levels of TNF-α, IL-1β, IL-18, IL-6, and IFN-γ were significantly increased in vivo and in vitro , compared to the control group. These pro-inflammatory cytokines had turned out to have a harmful effect on neurons, leading to neuronal apoptosis (Lu et al, 2005; Cai et al, 2014; Phuagkhaopong et al, 2017; Yin et al, 2017), which was confirmed by our present results.…”

Section: Discussionsupporting

confidence: 90%

Inhibitive Effects of FGF2/FGFR1 Pathway on Astrocyte-Mediated Inflammation in vivo and in vitro After Infrasound Exposure

Shi

Xiao

et al. 2018

Front. Neurosci.

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Infrasound, a kind of ambient noise, can cause severe disorders to various human organs, specially to central nervous system (CNS). Our previous studies have shown that infrasound-induced CNS injury was closely related with astrocytes activation and astrocytes-mediated neuroinflammation, but the underlying molecular mechanisms are still largely unclear. FGF2/FGFR1 (Fibroblast growth factor 2/Fibroblast growth factor receptor 1) pathway was reported to play an important role in anti-inflammation in CNS disorders. To further study the possible roles of FGF2/FGFR1 pathway in infrasound-induced CNS injury, here we exposed Sprague-Dawley rats or cultured astrocytes to 16 Hz, 150 dB infrasound, and explored the effects of FGF2 on infrasound-induced astrocytes activation and neuroinflammation. Western blotting, immunofluorescence and liquid chip method were used in this experiment. Our results showed that after 3- or 7-day exposure (2 h/day) of rats as well as 2 h exposure of cultured astrocytes to 16 Hz, 150 dB infrasound, astrocyte-expressed FGFR1 was downregulated in vivo and in vitro. FGF2 pretreatment not only inhibited infrasound-induced astrocyte activation in rat hippocampal CA1 region, but also reduced the levels of pro-inflammatory cytokines, such as TNF-α, IL-1β, IL-18, IL-6, and IFN-γ in vitro and in vivo. However, FGF2 significantly upregulated the expression of FGFR1. Furthermore, we showed that FGF2 could attenuate IκBα phosphorylation, NF-κB p65 translocation, pro-inflammatory cytokines levels, and neuronal loss in the CA1 region induced by infrasound. On the contrary, PD173074, a special antagonist of FGFR1, could reverse the effects above in vitro and in vivo. Taken together, our findings showed that FGF2/FGFR1 pathway may exert inhibitive effects on astrocyte-mediated neuroinflammation in vitro and in vivo after infrasound exposure.

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Section: Discussionsupporting

confidence: 90%

Inhibitive Effects of FGF2/FGFR1 Pathway on Astrocyte-Mediated Inflammation in vivo and in vitro After Infrasound Exposure

Shi

Xiao

et al. 2018

Front. Neurosci.

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“…On the other hand, pretreatment with curcumin significantly prevented these disturbances. Our result of NF-kB activation by cadmium exposure accords with data presented by Phuagkhaopong and coauthors in a study of cadmium chloride's effect in U-87 MG human astrocytoma cells and primary human (Phuagkhaopong et al, 2017). They have demonstrated increased secretion of interleukins IL-6 and IL-8, activation of NF-kB p65.…”

Section: Discussionsupporting

confidence: 91%

“…The neurotoxic effect of Cd in children was investigated in the 1970-1980s, but unfortunately the obtained results have received little attention since then. Recently, Phuagkhaopong and coauthors showed the evidence of Cd accumulation in U-87 MG astrocytoma cells model (Phuagkhaopong et al, 2017). Moreover, 24 hours exposure 10 µM CdCl 2 induced morphology disturbance of these glial cells and stimulated proinflammatory cellular response following IL-6 and IL-8 release.…”

Section: Introductionmentioning

confidence: 96%

Soluble curcumin prevents cadmium cytotoxicity in primary rat astrocytes by improving a lack of GFAP and glucose-6-phosphate-dehydrogenase

Nedzvetsky

Sukharenko

Kyrychenko

et al. 2018

Regul. Mech. Biosyst.

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Cadmium (Cd) is a heavy metal which is widespread in various environmental components. Moreover several occupational diseases have the complications that are related to Cd cytotoxicity. Low doses of Cd exposure could induce pathogenetic disturbances in several sensitive cells as result of its long biological half-life and accumulation in vital tissue types. Prolonged Cd exposure was determined as main factor in accumulation of this metal ion over time in the liver, kidneys and neural tissue cells. The neurotoxic effect of Cd was presented in several articles which reported both in vivo and in vitro study. One of the main causes of Cd neurotoxicity is the ability of this ion to increase the permeability of the blood brain barrier. Despite a focus of attention on Cd cytotoxicity over the last few decades, the effect of Cd in neural tissue cells has been presented in a limited number of articles. The neurotoxic effect of Cd is accompanied by biochemical changes as well as a lack of functional activity of the central nervous system. Taking into account that the cytotoxic effect of Cd is associated with oxidative stress, inflammation and selective cell death, antioxidants could be used to protect neural tissue cells against both chronic and acute Cd exposure. Antioxidants protect diverse cell types against metal induced cytotoxicity. Curcumin is a natural polyphenol which exhibits antioxidant and anti-inflammatory effect. Soluble forms of cucrcumin can penetrate the blood brain barrier and protect neural tissue cells against detrimental effects of cytotoxic compounds. Glial cells are the most numerous cell population in CNS. Astrocytes possess the ability to protect the neuronal cells against cytotoxicity and maintain CNS functions. The cytoskeleton of astrocytes is constructed with glial fibrillary acidic protein (GFAP). GFAP is involved in essential functions of astrocytes and reflects astrocyte reactivity. The molecular mechanisms of the neurotoxic effect of Cd on glial cytoskeleton remain unknown. Primary astrocyte cell culture was used as model to assess the gliotoxic effect of Cd as well as the potency of low doses of soluble curcumin to ameliorate the neurotoxic effect of Cd. The obtained results demonstrated depletion of GFAP and glucose-6-phosphate-dehydrogenase (G6PD) in astrocytes treated with 10 µM Cd. The exposure to 5 µM curcumin ameliorated the expression both of GFAP and G6PD in Cd suppressed astrocytes. Moreover, low doses of soluble curcumin significantly prevented the detrimental effects of Cd on cell viability and indices of oxidative stress. The obtained results are evidence that soluble forms of curcumin improve astrocyte viability, cytoskeleton depletion and glucose utilization pathway. Thus, soluble curcumin possesses a neuroprotective effect directed on astrocyte cytoskeleton and metabolic energy production.

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“…1d) and cadmium toxicity ( Fig. 1e), T cells transduced with our synthetic gene switches (3H-B1 to 7H-B1) were not activated and remained statistically identical to untransduced (UTD) controls up to concentrations above the ranges commonly used to test cellular responses to hypoxia and cadmium [46][47][48][49] (1000 µM CoCl2 and 500 µM CdCl2) ( Fig. 1d, e).…”

Section: Engineering Thermal-specific Gene Switchesmentioning

confidence: 90%

Remote control of CAR T cell therapies by thermal targeting

Miller

Sun

Harris

et al. 2020

Preprint

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The limited ability to control anti-tumor activity within tumor sites contributes to poor CAR T cell responses against solid malignancies. Systemic delivery of biologic drugs such as cytokines can augment CAR T cell activity despite off-target toxicity in healthy tissues that narrow their therapeutic window. Here we develop a platform for remote control of CAR T therapies by thermal targeting. To enable CAR T cells to respond to heat, we construct synthetic thermal gene switches that trigger expression of transgenes in response to mild elevations in local temperature (40-42 °C) but not to orthogonal cellular stresses such as hypoxia. We show that short pulses of heat (15-30 min) lead to more than 60-fold increases in gene expression without affecting key T cell functions including proliferation, migration, and cytotoxicity. We demonstrate thermal control of broad classes of immunostimulatory agents including CARs, Bispecific T cell Engagers (BiTEs), and cytokine superagonists to enhance proliferation and cell targeting. In mouse models of adoptive transfer, photothermal targeting of intratumoral CAR T cells to control the production of an IL-15 superagonist significantly enhances anti-tumor activity and overall survival. We envision that thermal targeting could improve the safety and efficacy of next-generation therapies by allowing remote control of CAR T cell activity.

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Cadmium-induced IL-6 and IL-8 expression and release from astrocytes are mediated by MAPK and NF-κB pathways

Cited by 99 publications

References 51 publications

Inhibitive Effects of FGF2/FGFR1 Pathway on Astrocyte-Mediated Inflammation in vivo and in vitro After Infrasound Exposure

Inhibitive Effects of FGF2/FGFR1 Pathway on Astrocyte-Mediated Inflammation in vivo and in vitro After Infrasound Exposure

Soluble curcumin prevents cadmium cytotoxicity in primary rat astrocytes by improving a lack of GFAP and glucose-6-phosphate-dehydrogenase

Remote control of CAR T cell therapies by thermal targeting

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