Evaluation of skin sensitization based on interleukin‑2 promoter activation in Jurkat cells

Nagahata, Taichi; Tsujino, Yoshio; Takayama, Eiji; Hikasa, H; Satoh, Ayano

doi:10.3892/br.2021.1486

Cited by 2 publications

(2 citation statements)

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“…Due to the complexity of this process, it is difficult to simulate the process completely in vitro. Equivalent alternatives for KE1-KE3 have been developed, but there is no effective alternative for KE4, so T cell activation is generally assessed indirectly by a local lymph node assay (LLNA) [48], gold standard in vivo method for skin sensitization. However, research on in vitro methods for detecting T cell activation or polarization is still ongoing, usually based on co-culture models of DC and T cells.…”

Section: T Cell Activation Assaymentioning

confidence: 99%

“…However, research on in vitro methods for detecting T cell activation or polarization is still ongoing, usually based on co-culture models of DC and T cells. Nagahata et al used Jurkat T cell lines (IL-2P::Jurkat cells) that stably express luciferin downstream of the pro-inflammatory cytokine IL-2 promoter, and assess skin sensitivity by luciferin activity [48]. This method can simultaneously monitor skin sensitization and the immune suppression of chemicals.…”

Section: T Cell Activation Assaymentioning

confidence: 99%

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Immunotoxicity In Vitro Assays for Environmental Pollutants under Paradigm Shift in Toxicity Tests

Wang

et al. 2022

IJERPH

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With the outbreak of COVID-19, increasingly more attention has been paid to the effects of environmental factors on the immune system of organisms, because environmental pollutants may act in synergy with viruses by affecting the immunity of organisms. The immune system is a developing defense system formed by all metazoans in the course of struggling with various internal and external factors, whose damage may lead to increased susceptibility to pathogens and diseases. Due to a greater vulnerability of the immune system, immunotoxicity has the potential to be the early event of other toxic effects, and should be incorporated into environmental risk assessment. However, compared with other toxicity endpoints, e.g., genotoxicity, endocrine toxicity, or developmental toxicity, there are many challenges for the immunotoxicity test of environmental pollutants; this is due to the lack of detailed mechanisms of action and reliable assay methods. In addition, with the strong appeal for animal-free experiments, there has been a significant shift in the toxicity test paradigm, from traditional animal experiments to high-throughput in vitro assays that rely on cell lines. Therefore, there is an urgent need to build high-though put immunotoxicity test methods to screen massive environmental pollutants. This paper reviews the common methods of immunotoxicity assays, including assays for direct immunotoxicity and skin sensitization. Direct immunotoxicity mainly refers to immunosuppression, for which the assays mostly use mixed immune cells or isolated single cells from animals with obvious problems, such as high cost, complex experimental operation, strong variability and so on. Meanwhile, there have been no stable and standard cell lines targeting immune functions developed for high-throughput tests. Compared with direct immunotoxicity, skin sensitizer screening has developed relatively mature in vitro assay methods based on an adverse outcome pathway (AOP), which points out the way forward for the paradigm shift in toxicity tests. According to the experience of skin sensitizer screening, this paper proposes that we also should seek appropriate nodes and establish more complete AOPs for immunosuppression and other immune-mediated diseases. Then, effective in vitro immunotoxicity assay methods can be developed targeting key events, simultaneously coordinating the studies of the chemical immunotoxicity mechanism, and further promoting the paradigm shift in the immunotoxicity test.

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Section: T Cell Activation Assaymentioning

confidence: 99%

Section: T Cell Activation Assaymentioning

confidence: 99%

Immunotoxicity In Vitro Assays for Environmental Pollutants under Paradigm Shift in Toxicity Tests

Wang

et al. 2022

IJERPH

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Alternative Methods for Skin-Sensitization Assessment

Gądarowska

Kalka

Daniel-Wójcik

et al. 2022

Toxics

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Skin sensitization is a term used to refer to the regulatory hazard known as allergic contact dermatitis (ACD) in humans or contact hypersensitivity in rodents, an important health endpoint considered in chemical hazard and risk assessments. Information on skin sensitization potential is required in various regulatory frameworks, such as the Directive of the European Parliament and the Council on Registration, Evaluation and Authorization of Chemicals (REACH). The identification of skin-sensitizing chemicals previously required the use of animal testing, which is now being replaced by alternative methods. Alternative methods in the field of skin sensitization are based on the measurement or prediction of key events (KE), i.e., (i) the molecular triggering event, i.e., the covalent binding of electrophilic substances to nucleophilic centers in skin proteins; (ii) the activation of keratinocytes; (iii) the activation of dendritic cells; (iv) the proliferation of T cells. This review article focuses on the current state of knowledge regarding the methods corresponding to each of the key events in skin sensitization and considers the latest trends in the development and modification of these methods.

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Evaluation of skin sensitization based on interleukin‑2 promoter activation in Jurkat cells

Cited by 2 publications

References 24 publications

Immunotoxicity In Vitro Assays for Environmental Pollutants under Paradigm Shift in Toxicity Tests

Immunotoxicity In Vitro Assays for Environmental Pollutants under Paradigm Shift in Toxicity Tests

Alternative Methods for Skin-Sensitization Assessment

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