Nature and kinetics of redox imbalance triggered by respiratory and skin chemical sensitizers on the human monocytic cell line THP-1
| العنوان: | Nature and kinetics of redox imbalance triggered by respiratory and skin chemical sensitizers on the human monocytic cell line THP-1 |
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| المؤلفون: | João D. Martins, Maria Teresa Cruz, Bruno Miguel Neves, Ana Silva, Isabel C.F.R. Ferreira |
| المصدر: | Redox Biology, Vol 16, Iss, Pp 75-86 (2018) Redox Biology |
| بيانات النشر: | Elsevier, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Mitochondrial ROS, HMOX1, Antioxidant, medicine.medical_treatment, Clinical Biochemistry, medicine.disease_cause, Dendritic cells maturation, Biochemistry, Antioxidants, Monocytes, Anhydrides, Cell Line, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, medicine, Humans, THP1 cell line, lcsh:QH301-705.5, Chemical respiratory allergy, Skin, Mitogen-Activated Protein Kinase Kinases, chemistry.chemical_classification, Reactive oxygen species, lcsh:R5-920, Organic Chemistry, ROS, Dendritic Cells, Glutathione, 3. Good health, Cell biology, Kinetics, 030104 developmental biology, chemistry, lcsh:Biology (General), Oxidative stress, 030220 oncology & carcinogenesis, Dinitrofluorobenzene, Allergic contact dermatitis, Signal transduction, Reactive Oxygen Species, lcsh:Medicine (General), Oxidation-Reduction, Heme Oxygenase-1, Research Paper |
| الوصف: | Low molecular weight reactive chemicals causing skin and respiratory allergies are known to activate dendritic cells (DC), an event considered to be a key step in both pathologies. Although generation of reactive oxygen species (ROS) is considered a major danger signal responsible for DC maturation, the mechanisms leading to cellular redox imbalance remain poorly understood. Therefore, the aim of this study was to unveil the origin and kinetics of redox imbalance elicited by 1-fluoro-2,4-dinitrobenzene (DNFB) and trimellitic anhydride chloride (TMAC), two golden standards of skin and chemical respiratory allergy, respectively. To track this goal, we addressed the time course modifications of ROS production and cellular antioxidant defenses as well as the modulation of MAPKs signaling pathways and transcription of pathophysiological relevant genes in THP-1 cells. Our data shows that the thiol-reactive sensitizer DNFB directly reacts with cytoplasmic glutathione (GSH) causing its rapid and marked depletion which results in a general increase in ROS accumulation. In turn, TMAC, which preferentially reacts with amine groups, induces a delayed GSH depletion as a consequence of increased mitochondrial ROS production. These divergences in ROS production seem to be correlated with the different extension of intracellular signaling pathways activation and, by consequence, with distinct transcription kinetics of genes such as HMOX1, IL8, IL1B and CD86. Ultimately, our observations may help explain the distinct DC phenotype and T-cell polarizing profile triggered by skin and respiratory sensitizers. Graphical abstract fx1 Highlights • Distinctive ROS origin and kinetics elicited by skin and respiratory sensitizers. • ROS production elicited by DNFB results primarily from direct GSH haptenation. • Distinct expression of genes involved in DC maturation and T-cell polarizing capacity. |
| اللغة: | English |
| تدمد: | 2213-2317 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::becc7a9e24c5f72125badca3103d925cTest http://www.sciencedirect.com/science/article/pii/S2213231717309187Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....becc7a9e24c5f72125badca3103d925c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 22132317 |
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