Mouse model of DNCB-induced atopic dermatitis

Hamad, Alshammari Fanar; Han, Jung-Geun; Rather, Irfan A.

doi:10.3329/bjp.v12i2.31950

Cited by 7 publications

(8 citation statements)

References 8 publications

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“…A mouse model similar to these diseases was used as a chronic inflammation model to validate in vitro results using TNFα or IFNγ treatment. So, we used DNCB solution ( 21 ) and IMQ cream ( 16 ) to establish these models and confirmed that the expression patterns of FRA1, c-JUN, HDAC1, and FLG in vivo were consistent with the in vitro data. These data suggest that normalizing the elevated expression levels of FRA1, c-JUN, or HDAC1 may be therapies for patients with AD or psoriasis.…”

Section: Discussionsupporting

confidence: 61%

“…We found that the AP1 binding motif in the FLG promoter is crucial for FLG down-regulation and that TNFα + IFNγ treatment induces the formation of a repressor complex between FRA1:c-JUN components of AP1 and histone deacetylase (HDAC) 1. We confirmed the altered expression of FLG and the FRA1:c-JUN:HDAC1 complex in vivo using mouse models of DNCB-induced AD ( 21 ) and IMQ-induced psoriasis ( 15 ).…”

supporting

confidence: 63%

“…To investigate whether TNFα and IFNγ were involved in mediating the suppression of the expression of FLG in vivo, we used a mouse model developed using topical application of DNCB to induce AD-like skin inflammation in BALB/c mice ( 21 ) ( SI Appendix , Fig. S2 A ).…”

Section: Resultsmentioning

confidence: 99%

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FRA1:c-JUN:HDAC1 complex down-regulates filaggrin expression upon TNFα and IFNγ stimulation in keratinocytes

Ahn

Yeo

Jung

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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Filaggrin (FLG), an essential structural protein for skin barrier function, is down-regulated under chronic inflammatory conditions, leading to disruption of the skin barrier. However, the detailed molecular mechanisms of how FLG changes in the context of chronic inflammation are poorly understood. Here, we identified the molecular mechanisms by which inflammatory cytokines inhibit FLG expression in the skin. We found that the AP1 response element within the –343/+25 of the FLG promoter was necessary for TNFα + IFNγ–induced down-regulation of FLG promoter activity. Using DNA affinity precipitation assay, we observed that AP1 subunit composition binding to the FLG promoter was altered from c-FOS:c-JUN (at the early time) to FRA1:c-JUN (at the late time) in response to TNFα + IFNγ stimulation. Knockdown of FRA1 or c-JUN abrogated TNFα + IFNγ–induced FLG suppression. Histone deacetylase (HDAC) 1 interacted with FRA1:c-JUN under TNFα + IFNγ stimulation. Knockdown of HDAC1 abrogated the inhibitory effect of TNFα + IFNγ on FLG expression. The altered expression of FLG, FRA1, c-JUN, and HDAC1 was confirmed in mouse models of 2,4-dinitrochlorobenzene–induced atopic dermatitis and imiquimod-induced psoriasis. Thus, the current study demonstrates that TNFα + IFNγ stimulation suppresses FLG expression by promoting the FRA1:c-JUN:HDAC1 complex. This study provides insight into future therapeutic strategies targeting the FRA1:c-JUN:HDAC1 complex to restore impaired FLG expression in chronic skin inflammation.

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Section: Discussionsupporting

confidence: 61%

supporting

confidence: 63%

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FRA1:c-JUN:HDAC1 complex down-regulates filaggrin expression upon TNFα and IFNγ stimulation in keratinocytes

Ahn

Yeo

Jung

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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“…A case-control study was done on 80 male Albino mice (20-30g) recruited from local markets, were treated with 1-Chloro-2,4-dinitrobenzene (DNCB)induced atopic dermatitis (Hamad et al, 2017) and compared with age and the sex-matched control group comprised of 20 healthy male Albino mice. The study was started in June and inished in December 2019.…”

Section: Methodsmentioning

confidence: 99%

The Effect of Topical Dapsone In Comparison With Tacrolimus On Dncb Induced Atopic Dermatitis In Mice

Yousif¹,

Abu-Raghif²

2020

ijrps

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To assess the effect of topical dapsone in the treatment of atopic dermatitis in comparison with tacrolimus. A case-control study was done on 80 male Albino mice (20-30g) recruited from local markets, were treated with 1-Chloro-2,4-dinitrobenzene (DNCB)-induced atopic dermatitis and compared with age and the sex-matched control group comprised of 20 healthy male Albino mice. The topical applications of Tacrolimus 0.1% ointment and Dapsone 5% gel were performed on atopic dermatitis area for seven days and fourteen days once daily starting from the fourth day of induction and Complete blood count, IL-4 and IL-13 were measured in skin tissue homogenate in addition to histopathological evaluation of atopic dermatitis skin lesion and assessment of observational severity score and compared with those of controls. The results revealed that the levels of IL-4 and IL-13, total WBC, observational severity score, and the score of all histopathological markers were increased significantly in the group of mice treated with 1-Chloro-2,4-dinitrobenzene (DNCB) for A.D. induction in comparison with controls. These markers were reduced significantly after the topical application of tacrolimus. They showed a comparable reduction but after a longer duration of topical treatment with dapsone after two weeks of treatment. Topical application of dapsone on induced A.D. mice showed a significant reduction in the levels of IL-4 and IL-13, total WBC, observational severity score, and histopathological markers score and these effects were compared to those of topical tacrolimus.

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“…When applied repeatedly to the skin, DNCB induces Th2-dominant immune response, causing elevation of serum IgE levels, overproduction of keratinocytes, and in ltration of mast cells. Among diverse substances that cause AD, DNCB is frequently used in AD research owing to it being affordable and its results being reproducible [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

The Inhibitory Effect of Human Placenta Extract (Laennec ® ) on Atopic Dermatitis-Like Skin Disease In Vivo and In Vitro

Jeong

Jeon

Jing

et al. 2023

Preprint

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Atopic dermatitis (AD) is an allergic inflammatory skin disease accompanied by severe itching and eczema. Human placenta extract (PE), used for treatment of conditions related to hepatic function, possess anti-inflammatory and antiviral properties. In this study, we investigated the efficacy of PE against AD in a 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse model, and in tumor necrosis factor (TNF)-α/interferon (IFN)-γ-stimulated human keratinocytes (HaCaT) and immunized splenocytes. We confirmed that subcutaneous administration of PE (200 or 400 µL, twice a week) improved AD skin lesions and reduced the spleen index in mice. In addition, the expression levels of immune-related and proinflammatory factors were suppressed in serum and skin tissue. These results were consistent with the tendency observed in HaCaT cells and splenocytes. Intriguingly, human-derived PE had no side effects, such as loss of muscle mass, compared to corticosteroid, which was used as a positive control. Taken together, our results demonstrate that PE effectively inhibits the development of AD and might be a potentially useful therapeutic agent for AD-like skin disease.

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Mouse model of DNCB-induced atopic dermatitis

Cited by 7 publications

References 8 publications

FRA1:c-JUN:HDAC1 complex down-regulates filaggrin expression upon TNFα and IFNγ stimulation in keratinocytes

FRA1:c-JUN:HDAC1 complex down-regulates filaggrin expression upon TNFα and IFNγ stimulation in keratinocytes

The Effect of Topical Dapsone In Comparison With Tacrolimus On Dncb Induced Atopic Dermatitis In Mice

The Inhibitory Effect of Human Placenta Extract (Laennec ® ) on Atopic Dermatitis-Like Skin Disease In Vivo and In Vitro

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