Time course of skin features and inflammatory biomarkers after liquid sulfur mustard exposure in SKH-1 hairless mice

Mouret, Stéphane; Wartelle, Julien; Batal, Mohamed; Emorine, Sandy; Bertoni, Marine; Poyot, Thomas; Cléry-Barraud, Cécile; Bakdouri, Nacera El; Peinnequin, André; Douki, Thierry; Boudry, Isabelle

doi:10.1016/j.toxlet.2014.09.022

Cited by 29 publications

(28 citation statements)

References 73 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…49,50 Additionally, the clinical, histopathological, and immunohistochemical evaluation of the skin pathologic lesions inflicted by NM in SKH-1 hairless and C57BL/6 mice show that these lesions and their progression are comparable to those reported from SM exposure in humans and other animal models, including hairless mice. 36,[49][50][51] Since hairless mouse is a superior murine model to study skin lesions and has been reported as a reliable model for investigating SMinduced skin toxicity, 36,51,52 our completed studies in this mouse model with NM provide a valuable tool to further investigate mechanisms mediating vesicant-induced skin toxicity and conduct accelerated efficacy studies to identify and optimize effective targeted therapies.…”

Section: Clinicopathological and Molecular Toxicity Of Mustard Vesicamentioning

confidence: 99%

Mustard vesicating agent–induced toxicity in the skin tissue and silibinin as a potential countermeasure

Tewari‐Singh

Agarwal

2016

Annals of the New York Academy of Sciences

View full text Add to dashboard Cite

Exposure to the vesicating agents sulfur mustard (SM) and nitrogen mustard (NM) causes severe skin injury with delayed blistering. Depending upon the dose and time of their exposure, edema and erythema develop into blisters, ulceration, necrosis, desquamation, and pigmentation changes, which persist weeks and even years after exposure. Research advances have generated data that have started to explain the probable mechanism of action of vesicant-induced skin toxicity; however, despite these advances, effective and targeted therapies are still deficient. This review highlights studies on two SM analogs, chloroethyl ethyl sulfide (CEES) and NM, and CEES- and NM-induced skin injury mouse models that have substantially added to the knowledge on the complex pathways involved in mustard vesicating agent–induced skin injury. Furthermore, employing these mouse models, studies under the National Institutes of Health Countermeasures Against Chemical Threats program have identified the flavanone silibinin as a novel therapeutic intervention with the potential to be developed as an effective countermeasure against skin injury following exposure to mustard vesicating agents.

show abstract

Section: Clinicopathological and Molecular Toxicity Of Mustard Vesicamentioning

confidence: 99%

Mustard vesicating agent–induced toxicity in the skin tissue and silibinin as a potential countermeasure

Tewari‐Singh

Agarwal

2016

Annals of the New York Academy of Sciences

View full text Add to dashboard Cite

show abstract

“…These findings are consistent with a role for inflammatory mediators in tissue injury. 24 In keratinocytes, we also found that COX-2, which generates prostaglandin E2, was upregulated after SM exposure, along with inducible nitric oxide synthase, which generates nitric oxide, and galectin-3, a galactoside-binding protein whose expression and secretion are important in controlling proliferation, cell adhesion, and migration. 25,26 This is important, as it is well recognized that inflammatory mediators and growth factors generated by keratinocytes can contribute to inflammation, the resolution of inflammation, and wound healing.…”

Section: Upregulation Of Mediators Of Inflammation In the Skin Followmentioning

confidence: 68%

“…In SM‐exposed skin, we have identified mustard‐induced modulation of mediators, including IL‐1β, IL‐6, tumor necrosis factor α, cyclooxygenase‐2 (COX‐2), and vascular cell adhesion molecule. These findings are consistent with a role for inflammatory mediators in tissue injury …”

Section: Upregulation Of Mediators Of Inflammation In the Skin Followmentioning

confidence: 78%

“…Myeloid‐derived mast cells are degranulated in mouse skin following exposure to SM . Mast cells release a variety of mediators that contribute not only to inflammation but also to wound healing and angiogenesis, including serine proteases, histamine, eicosanoids, and various cytokines .…”

Section: Upregulation Of Mediators Of Inflammation In the Skin Followmentioning

confidence: 87%

“…[27][28][29] Myeloid-derived mast cells are degranulated in mouse skin following exposure to SM. 10,24 Mast cells release a variety of mediators that contribute not only to inflammation but also to wound healing and angiogenesis, including serine proteases, histamine, eicosanoids, and various cytokines. 30 As many of these mediators play roles in mustard-induced skin injury, inhibitors of mast cell degranulation have been proposed as potential countermeasures.…”

Section: Upregulation Of Mediators Of Inflammation In the Skin Followmentioning

confidence: 99%

See 2 more Smart Citations

Tissue injury and repair following cutaneous exposure of mice to sulfur mustard

Joseph

Composto

Heck

2016

Annals of the New York Academy of Sciences

View full text Add to dashboard Cite

In mouse skin, sulfur mustard is a potent vesicant, damaging both the epidermis and the dermis. The extent of wounding is dependent on the dose of sulfur mustard and the duration of exposure. Initial responses include erythema, pruritus, edema, and xerosis; this is followed by an accumulation of inflammatory leukocytes in the tissue, activation of mast cells, and the release of mediators, including proinflammatory cytokines and bioactive lipids. These proinflammatory mediators contribute to damaging the epidermis, hair follicles, and sebaceous glands and to disruption of the epidermal basement membrane. This can lead to separation of the epidermis from the dermis, resulting in a blister, which ruptures, leading to the formation of an eschar. The eschar stimulates the formation of a neoepidermis and wound repair and may result in persistent epidermal hyperplasia. Epidermal damage and repair is associated with upregulation of enzymes generating proinflammatory and progrowth/pro–wound healing mediators, including cyclooxygenase-2 (COX-2), which generates prostanoids, inducible nitric oxide synthase (iNOS), which generates nitric oxide, fibroblast growth factor receptor 2 (FGFR2), and galectin-3. Characterization of the mediators regulating structural changes in the skin during sulfur mustard–induced tissue damage and wound healing will aid in the development of therapeutic modalities to mitigate toxicity and stimulate tissue repair processes.

show abstract

Expression of Laminin γ2 Proteolytic Fragments in Murine Skin Following Exposure to Sulfur Mustard

Chang

Wang

Chang

et al. 2020

The Anatomical Record

View full text Add to dashboard Cite

Laminin-332 is a basement membrane protein composed of three genetically distinct polypeptide chains that actively promote both skin epidermal cell adhesion and migration. Proteolytic fragments of the laminin γ2 chain stimulate migration and scattering of keratinocytes and cancer cells. Sulfur mustard (SM) is a bifunctional alkylating agent that induces separation of basal keratinocytes from the dermal-epidermal junction and invokes a strong inflammatory response leading to delayed wound repair. In the present studies, the role of laminin γ2 in SM-induced skin injury and wound repair was investigated using the mouse ear vesicant model. We found that laminin γ2 chain mRNA was preferentially upregulated in mouse ear skin exposed to SM. In situ hybridization confirmed overexpression of laminin γ2 transcript. Western blot analysis showed increased protein expression of the full-length proform of laminin γ2 and smaller processed fragments of laminin γ2 in skin exposed to SM. Dual immunofluorescence labeling indicated that laminin γ2 fragments are prevalent in suprabasal keratinocytes behind the leading edge in areas of hyperplasia in injured skin. In addition, co-expression of laminin γ2 and the senescent marker, p16 INK4a was found to overlap with the hyperplastic migratory epithelial sheet. This observation is similar to hypermotile keratinocytes reported in invasive carcinoma cells. Overall, our studies indicate that laminin γ2 is preferentially expressed in skin post SM exposure and that protein expression appears to become progressively more fragmented. The laminin γ2 fragments may play a role in regulating SM-induced skin wound repair. Anat

show abstract

Time course of skin features and inflammatory biomarkers after liquid sulfur mustard exposure in SKH-1 hairless mice

Cited by 29 publications

References 73 publications

Mustard vesicating agent–induced toxicity in the skin tissue and silibinin as a potential countermeasure

Mustard vesicating agent–induced toxicity in the skin tissue and silibinin as a potential countermeasure

Tissue injury and repair following cutaneous exposure of mice to sulfur mustard

Expression of Laminin γ2 Proteolytic Fragments in Murine Skin Following Exposure to Sulfur Mustard

Contact Info

Product

Resources

About