Zinc- and Copper-Induced Interleukin-6 Release in Primary Cell Cultures From Rat Heart

Ansteinsson, Vibeke; Refsnes, Magne; Skomedal, Tor; Osnes, Jan‐Bjørn; Schiander, I.; Låg, Marit

doi:10.1007/s12012-009-9043-5

Cited by 14 publications

(6 citation statements)

References 45 publications

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“…Several metals such as zinc (Zn), arsenic (As), nickel (Ni), iron (Fe), copper (Cu), vanadium (V) manganese (Mn), lead (Pb), and cadmium (Cd) have been associated with health effects induced by PM [ 178 , 179 ]. Various particle-associated metals have been reported to activate MAPKs and NF-κB signaling in bronchial epithelial cells and other cell types, and may thereby affect the expression of cytokines and chemokines as well as other proinflammatory genes [ 180 , 181 , 182 , 183 ]. Generation of oxidative stress has been considered as one of the major mechanisms behind heavy metal toxicity, as already discussed, and heavy metals have been shown to disturb signal pathways and modulate transcription factors important in regulation of cytokines [ 184 , 185 ].…”

Section: Molecular Initiating Events: Triggering Mechanisms For Pamentioning

confidence: 99%

Activation of Proinflammatory Responses in Cells of the Airway Mucosa by Particulate Matter: Oxidant- and Non-Oxidant-Mediated Triggering Mechanisms

et al. 2015

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Inflammation is considered to play a central role in a diverse range of disease outcomes associated with exposure to various types of inhalable particulates. The initial mechanisms through which particles trigger cellular responses leading to activation of inflammatory responses are crucial to clarify in order to understand what physico-chemical characteristics govern the inflammogenic activity of particulate matter and why some particles are more harmful than others. Recent research suggests that molecular triggering mechanisms involved in activation of proinflammatory genes and onset of inflammatory reactions by particles or soluble particle components can be categorized into direct formation of reactive oxygen species (ROS) with subsequent oxidative stress, interaction with the lipid layer of cellular membranes, activation of cell surface receptors, and direct interactions with intracellular molecular targets. The present review focuses on the immediate effects and responses in cells exposed to particles and central down-stream signaling mechanisms involved in regulation of proinflammatory genes, with special emphasis on the role of oxidant and non-oxidant triggering mechanisms. Importantly, ROS act as a central second-messenger in a variety of signaling pathways. Even non-oxidant mediated triggering mechanisms are therefore also likely to activate downstream redox-regulated events.

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Section: Molecular Initiating Events: Triggering Mechanisms For Pamentioning

confidence: 99%

Activation of Proinflammatory Responses in Cells of the Airway Mucosa by Particulate Matter: Oxidant- and Non-Oxidant-Mediated Triggering Mechanisms

et al. 2015

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“…For example, zinc and copper caused release of IL-6 from cardiomyocytes and cardiac fibroblasts at micromolar concentration. 51 Expression of MCP1 has been shown to be elevated by iron 52 and silica; 53 of note, flaming cardboard caused upregulation of MCP1 within 4 h of exposure. Hence, we hypothesize that the enhanced effects of cardboard smoke condensate on inflammatory cytokine secretion in HAECs are driven by PAHs and inorganic elements that are not as abundant in plastic smoke condensates.…”

Section: ■ Discussionmentioning

confidence: 99%

“…Previous literature reports adverse effects of several inorganic elements on cellular health. For example, zinc and copper caused release of IL-6 from cardiomyocytes and cardiac fibroblasts at micromolar concentration . Expression of MCP1 has been shown to be elevated by iron and silica; of note, flaming cardboard caused upregulation of MCP1 within 4 h of exposure.…”

Section: Discussionmentioning

confidence: 99%

Burn Pit Smoke Condensate-Mediated Toxicity in Human Airway Epithelial Cells

Ghosh,

Payton,

Gallant

et al. 2024

Chem. Res. Toxicol.

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Burn pits are a method of open-air waste management that was common during military operations in Iraq, Afghanistan, and other regions in Southwest Asia. Veterans returning from deployment have reported respiratory symptoms, potentially from exposure to burn pit smoke, yet comprehensive assessment of such exposure on pulmonary health is lacking. We have previously shown that exposure to condensates from burn pit smoke emissions causes inflammation and cytotoxicity in mice. In this study, we explored the effects of burn pit smoke condensates on human airway epithelial cells (HAECs) to understand their impact on cellular targets in the human lung. HAECs were cultured at the air–liquid interface (ALI) and exposed to burn pit waste smoke condensates (plywood, cardboard, plastic, mixed, and mixed with diesel) generated under smoldering and flaming conditions. Cytotoxicity was evaluated by measuring transepithelial electrical resistance (TEER) and lactate dehydrogenase (LDH) release; toxicity scores (TSs) were quantified for each exposure. Pro-inflammatory cytokine release and modulation of gene expression were examined for cardboard and plastic condensate exposures. Burn pit smoke condensates generated under flaming conditions affected cell viability, with flaming mixed waste and plywood exhibiting the highest toxicity scores. Cardboard and plastic smoke condensates modulated cytokine secretion, with GM-CSF and IL-1β altered in more than one exposure group. Gene expression of detoxifying enzymes (ALDH1A3, ALDH3A1, CYP1A1, CYP1B1, NQO1, etc.), mucins (MUC5AC, MUC5B), and cytokines was affected by several smoke condensates. Particularly, expression of IL6 was elevated following exposure to all burn pit smoke condensates, and polycyclic aromatic hydrocarbon acenaphthene was positively associated with the IL-6 level in the basolateral media of HAECs. These observations demonstrate that exposure to smoke condensates of materials present in burn pits adversely affects HAECs and that aberrant cytokine secretion and altered gene expression profiles following burn pit material smoke exposure could contribute to the development of airway disease.

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“…As IL-6 is a precursor of CRP [61], larger stressor-evoked IL-6 responses over time may cause heightened systemic levels of CRP [62]. Experimental study based on rat cardiac cells suggested that copper seemed to induce IL-6 release through enhancing signaling pathways that normally regulate the basal IL-6 release [63]. Copper and IL6R variant may interact through increase of levels of IL-6, and so as to increase levels of CRP.…”

Section: Discussionmentioning

confidence: 99%

Multiple plasma metals, genetic risk and serum C-reactive protein: A metal-metal and gene-metal interaction study

et al. 2020

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BackgroundC-reactive protein (CRP) is a well-recognized biomarker of inflammation, which can be used as a predictor of cardiovascular disease. Evidence have suggested exposure to multiple metals/metalloids may affect immune system and give rise to cardiovascular disease. However, it is lack of study to comprehensively evaluate the association of multiple metals and CRP, the interactions between metals, and the gene-metal interaction in relation to CRP levels.AimsTo explore the associations of multiple plasma metals with serum CRP, and to test the interactions between metals, and gene-metal interactions on the levels of serum CRP.MethodsWe included 2882 participants from the Dongfeng-Tongji cohort, China, and measured 23 plasma metals and serum CRP concentrations. The genetic risk score (GRS) was calculated based on 7 established CRP-associated variants. For metals which were associated with the levels of CRP, we further tested the interactions between metals on CRP, and analyzed the gene-metal interactions on CRP.ResultsThe median level for CRP in the total population was 1.17 mg/L. After multivariable adjustment, plasma copper was positively associated with serum CRP (FDR < 0.001), whereas selenium was negatively associated with serum CRP (FDR = 0.01). Moreover, selenium and zinc attenuated the positive association between high plasma copper and CRP (P for interaction < 0.001). Participants with a higher GRS had a higher CRP level, with the increase in ln-transformed CRP per increment of 5 risk alleles were 0.64 for weighted GRS, and 0.54 for unweighted GRS (both P < 0.001). Furthermore, the genetic association with CRP was modified by copper concentration (P for interaction < 0.001).ConclusionsOur results suggest that serum CRP is positively associated with plasma concentration of copper, and inversely associated with selenium. Plasma zinc, selenium and CRP genetic predisposition would modify the associations between plasma copper and serum CRP.

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Zinc- and Copper-Induced Interleukin-6 Release in Primary Cell Cultures From Rat Heart

Cited by 14 publications

References 45 publications

Activation of Proinflammatory Responses in Cells of the Airway Mucosa by Particulate Matter: Oxidant- and Non-Oxidant-Mediated Triggering Mechanisms

Activation of Proinflammatory Responses in Cells of the Airway Mucosa by Particulate Matter: Oxidant- and Non-Oxidant-Mediated Triggering Mechanisms

Burn Pit Smoke Condensate-Mediated Toxicity in Human Airway Epithelial Cells

Multiple plasma metals, genetic risk and serum C-reactive protein: A metal-metal and gene-metal interaction study

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