Keratinocytes: innate immune cells in atopic dermatitis

Chieosilapatham, Panjit; Kiatsurayanon, Chanisa; Umehara, Yoshie; Trujillo-Paez, Juan Valentin; Peng, Ge; Yue, Hainan; Nguyen, Ly; Niyonsaba, François

doi:10.1111/cei.13575

Cited by 108 publications

(85 citation statements)

References 104 publications

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“…We also found that triggered pyroptotic cell death of keratinocytes was suppressed by mdivi‐1, Keratinocyte pyroptosis might affect AD in two aspects including barrier disruption, and the release of the pro‐inflammatory cytokines IL‐1β and IL‐18 aggravating the development of AD. IL‐1β and IL‐18 promote the chemotaxis of inflammatory cells and regulate TH2 cytokine production and histamine 25,26 . Our in vitro results at least demonstrated the suppressive role of mdivi‐1 in the activation NLRP3 inflammasomes and pyroptosis in the keratinocytes under AD‐like conditions.…”

Section: Discussionmentioning

confidence: 55%

Mdivi‐1 alleviates atopic dermatitis through the inhibition of NLRP3 inflammasome

Liu

et al. 2021

Experimental Dermatology

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Atopic dermatitis (AD) is a chronic inflammatory cutaneous disorder with few treatment options. Dynamin‐related protein 1 (Drp1)‐dependent mitochondrial fission contributes to the activation of NLRP3 inflammasome, and inhibiting Drp1 has been become an attractive therapeutic strategy for inflammatory diseases. This study aimed to investigate the effects of Drp1 inhibitor mdivi‐1 on experimental AD. We firstly detected the effects of mdivi‐1 on primary human keratinocytes in an inflammatory cocktail‐induced AD‐related inflammation in vitro. Results showed that mdivi‐1 inhibited NLRP3 inflammasome activation and pyroptosis which were evidenced by decreased expression of NLRP3, ASC, cleavage of caspase‐1, GSDMD‐NT, mature interleukin (IL)‐1β and IL‐18 in keratinocytes under AD‐like inflammation. Next, mouse model of AD‐like skin lesions was induced by epicutaneous application of 2,4‐dinitrochlorobenzene (DNCB) and mdivi‐1 (25 mg/kg/day, days 5–33 during construction of AD model) was intraperitoneally injected into DNCB‐induced mice. AD mice with mdivi‐1 treatment exhibited ameliorated AD symptoms, lower serum IgE level, and reduced epidermal thickening, mast cells infiltration, and production of IL‐4, IL‐5 and IL‐13 in the lesional tissues. Indeed, mdivi‐1 significantly inhibited NLRP3 inflammasome activation and pyroptotic injury occurred in DNCB‐treated skin tissues. Mechanically, mdivi‐1 regulated the expression of mitochondrial dynamic proteins and suppressed the activation of NF‐κB signal pathway which is an upstream of NLRP3 inflammasome both in vitro and in vivo. This study demonstrated that mdivi‐1 could protect against experimental AD through inhibiting the activation of NLRP3 inflammasome and subsequent inflammatory cytokine release, and mdivi‐1 might exert this function by inhibiting mitochondrial fission and subsequently blocking NF‐κB pathway.

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Section: Discussionmentioning

confidence: 55%

Mdivi‐1 alleviates atopic dermatitis through the inhibition of NLRP3 inflammasome

Liu

et al. 2021

Experimental Dermatology

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“…In the keratinocytes of AD patients, the expression and secretion of cytokines IL-25, IL-33, and TSLP, and the chemokines TARC, MDC, and RANTES, which are directly or indirectly related to the activation of Th2 cells, are increased [ 64 ]. In addition, expression of CCR4, a receptor for TARC and MDC, increases on the surface of Th2 cells, thereby increasing Th2 cell invasion and activity [ 29 , 65 ].…”

Section: Discussionmentioning

confidence: 99%

Lithospermum erythrorhizon Alleviates Atopic Dermatitis-like Skin Lesions by Restoring Immune Balance and Skin Barrier Function in 2.4-Dinitrochlorobenzene-Induced NC/Nga Mice

Lee

Choung

2021

Nutrients

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The incidence of atopic dermatitis (AD), a disease characterized by an abnormal immune balance and skin barrier function, has increased rapidly in developed countries. This study investigated the anti-atopic effect of Lithospermum erythrorhizon (LE) using NC/Nga mice induced by 2,4-dinitrochlorobenzene. LE reduced AD clinical symptoms, including inflammatory cell infiltration, epidermal thickness, ear thickness, and scratching behavior, in the mice. Additionally, LE reduced serum IgE and histamine levels, and restored the T helper (Th) 1/Th2 immune balance through regulation of the IgG1/IgG2a ratio. LE also reduced the levels of AD-related cytokines and chemokines, including interleukin (IL)-1β, IL-4, IL-6, tumor necrosis factor-α (TNF-α), thymic stromal lymphopoietin, thymus and activation-regulated chemokine, macrophage-derived chemokine, regulated on activation, normal T cell expressed and secreted, and monocyte chemoattractant protein-1 in the serum. Moreover, LE modulated AD-related cytokines and chemokines expressed and secreted by Th1, Th2, Th17, and Th22 cells in the dorsal skin and splenocytes. Furthermore, LE restored skin barrier function by increasing pro-filaggrin gene expression and levels of skin barrier-related proteins filaggrin, involucrin, loricrin, occludin, and zonula occludens-1. These results suggest that LE is a potential therapeutic agent that can alleviate AD by modulating Th1/Th2 immune balance and restoring skin barrier function.

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“…Keratinocytes such as HaCaT cells play central roles in skin disease, the initiation and maintenance of AD (Chieosilapatham et al 2021 ). Therefore, HaCaT cells are commonly used for the in vitro testing of anti-inflammatory and anti-atopic skin agents (Colombo et al 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Purple corn extract alleviates 2,4-dinitrochlorobenzene-induced atopic dermatitis-like phenotypes in BALB/c mice

Nam

Seo

et al. 2021

Animal Cells and Systems

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Zea mays L. (Poaceae), also known as purple corn, is an annual herbaceous plant that is grown as food for human consumption in a variety of forms, including cooking oils and sweeteners in processed food and beverage products. The purpose of this study was to determine whether a novel purple corn extract, FB801, might have an anti-atopic dermatitis (AD) effect on AD-like skin lesions induced by 2,4-dinitrochlorobenzene (DNCB) in BALB/c mice. Topical sensitization (1%) and challenge (0.3%) by DNCB were performed on the dorsal skin and right ear of BALB/c mice to induce AD. Following FB801 and dexamethasone administered orally, the severity of skin lesions was examined macroscopically and histologically. Serum levels of immunoglobulin E (IgE) and various cytokines were determined by enzyme-linked immunosorbent assay. Oral administration of FB801 significantly reduced typical symptoms of AD (erythema/bleeding, swelling, molting/erosion and scaling/drying), scratching frequencies, and the recruitment of inflammatory and mast cells. In addition, FB801 suppressed serum levels of IgE and T helper (Th)2 type cytokines such as interleukin (IL)-4 and IL-10 in DNCB-treated BALB/c mice. Furthermore, FB801 reduced the degradation of inhibitor of nuclear factor-κB proteins (NF-κB) in tumor necrosis factor (TNF)-α-stimulated human keratinocyte (HaCaT) cells. These results suggest that FB801 inhibited the development of the AD-like skin symptoms by regulating Th1 and Th2 responses in the skin lesions in mice and suppressing TNF-α induced NF-κB activation in HaCaT cells, suggesting that FB801 has potential application as an effective alternative therapy for the prevention and management of AD.

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Keratinocytes: innate immune cells in atopic dermatitis

Cited by 108 publications

References 104 publications

Mdivi‐1 alleviates atopic dermatitis through the inhibition of NLRP3 inflammasome

Mdivi‐1 alleviates atopic dermatitis through the inhibition of NLRP3 inflammasome

Lithospermum erythrorhizon Alleviates Atopic Dermatitis-like Skin Lesions by Restoring Immune Balance and Skin Barrier Function in 2.4-Dinitrochlorobenzene-Induced NC/Nga Mice

Purple corn extract alleviates 2,4-dinitrochlorobenzene-induced atopic dermatitis-like phenotypes in BALB/c mice

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