Barrier abnormalities and keratinocyte-derived cytokine cascade after cessation of long-term topical glucocorticosteroid on hairless mouse skin

Lin, Tzu Kai; Wei, Kai; Wu, Chin Han; Lai, Feng‐Jie; Lan, C.‐C. E.; Chang, Chung Hsing; Peng, A; Tsai, Jui Chen; Sheu, Hamm Ming

doi:10.1016/j.dsi.2015.05.002

Cited by 5 publications

(6 citation statements)

References 39 publications

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“…The pathogenesis of HDD is not fully understood, but it is mainly believed to be related to the breakdown of the skin barrier. Long-term topical application of corticosteroids inhibits normal epidermal differentiation and reduces the synthesis of structural components of epidermal terminal differentiation, such as total protein and fibrillin, ultimately causing skin barrier function defects [ 10 ]. The results of this study showed that after 7 weeks of topical clobetasol propionate, the model was successfully established, the epidermal tissue-related proteins FLG, LOR, and Caspase-14 were downregulated, transdermal water loss (TEWL) increased, skin moisture, decreased oil content, manifested as dryness, desquamation, etc.…”

Section: Discussionmentioning

confidence: 99%

“…Another key protein, filaggrin (FLG), is processed by cysteine protease-14 (Caspase-14), cut and catabolize into free amino acids, provide skin with natural moisturizing factors, and maintain skin moisture [ 8 ]. HDD is characterized by disruption of skin barrier-associated proteins, and with the disruption of the skin barrier, a keratinocyte-derived inflammatory cascade is initiated, and T helper cells and eosinophils are increased [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

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The Effect and Mechanism of Burnet Gels on Steroid-Dependent Dermatitis in Guinea Pig Model

et al. 2022

BioMed Research International

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Objective. This study was designed to establish quality standards of Burnet gels and investigate the effects and mechanism of Burnet gels on steroid-dependent dermatitis (HDD) in guinea pigs. Methods. HPLC was used to determine the content of gallic acid, Gentiopicrin, and paeonol. A total of 48 male guinea pigs were recruited and randomly divided into control group, model group, tacrolimus ointment group, and Burnet gel group (Low, medium, and high concentration). The HDD guinea pig model was established by the 0.5% clobetasol propionate tincture. After HDD model establishment, control group and model group smeared normal saline and the rest of the group with corresponding drugs for three weeks. The contents of IFN-γ, IL-4, and IgE in the guinea pig serum were detected by the ELISA; the protein expression levels of FLG, LOR, and Caspase-14 in the epidermis of guinea pigs were detected by the immunohistochemical and Western blotting method. Results. The content of gallic acid, Gentiopicrin, and paeonol was 0.30 mg/g, 1.06 mg/g, and 0.56 mg/g. Compared with the normal group, the IFN-γ, IL-4, and IgE of guinea pig serum in the model group were significantly increased; the FLG, LOR, and Caspase-14 of guinea pig epidermis in the model group were significantly decreased; compared with the model group, the IFN-γ, IL-4, and IgE of guinea pig serum in the tacrolimus ointment group and Burnet gel group were significantly decreased; the FLG, LOR, and Caspase-14 of guinea pig epidermis in the tacrolimus ointment group and Burnet gel group were significantly increased. Conclusion. Burnet gels can improve guinea pig HDD model, and the mechanism may be related to inhibiting skin inflammation and promoting the formation of epidermal skin barrier.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Effect and Mechanism of Burnet Gels on Steroid-Dependent Dermatitis in Guinea Pig Model

et al. 2022

BioMed Research International

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“…The initiation of these early inflammatory processes leads to the activation of resident cells from the adaptive immune system, infiltration of circulating immune cells and, ultimately, to the beginning of a chronic skin inflammation. Accordingly, topical corticosteroid-induced skin barrier impairment may trigger inflammatory responses in a rebound effect via the increased activity of NF-kB, which is suppressed by the anti-inflammatory action of corticosteroids during treatment but appears after its cessation [ 19 ]. In contrast, VDR agonists have been shown to inhibit NF-kB activity [ 20 ] and consequently the secretion of IL-1α and IL-8 by human keratinocytes [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

Calcipotriol/Betamethasone Dipropionate Foam Inhibits Th17 Cytokine Secretion and Improves Epidermal Barrier Markers in a Human Th17 Skin Inflammation Model

Lovato

Hebsgaard

et al. 2021

Dermatol Ther (Heidelb)

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Introduction T-helper 17 (Th17) cytokines play a key role in the pathophysiology of psoriasis by driving inflammatory responses that lead to epidermal alterations. Markers of epidermal differentiation, including the proteins loricrin (LOR), filaggrin (FLG) and involucrin (IVL), are dysregulated in psoriatic skin. The fixed-dose combination of calcipotriol/betamethasone dipropionate (Cal/BD) foam and clobetasol propionate (CP) are widely used, effective topical treatments for psoriasis. In this study, we investigated the effects of Cal/BD foam and CP cream on Th17 cytokine secretion and epidermal differentiation using a human Th17 skin inflammation model (InflammaSkin®). Methods The fixed-dose combination Cal/BD foam and the CP cream were applied once and twice daily, respectively, onto the air-exposed epidermal surface of InflammaSkin cultures for 7 days. Th17 cytokine levels were measured in culture supernatants, and gene expression analysis and immunohistochemical staining for LOR, FLG and IVL were performed on the skin samples. Results Topical treatment with Cal/BD foam almost completely inhibited Th17 cytokine secretion and upregulated LOR and IVL expression, but not FLG expression, at the mRNA and protein levels. Topical treatment with CP cream significantly reduced Th17 cytokine levels, but to a lesser extent than Cal/BD foam, and did not improve expression of any of the epidermal differentiation markers. Conclusion Compared with CP treatment, the fixed-dose combination Cal/BD foam showed a greater suppression of Th17 cytokine secretion and improved epidermal differentiation, resulting in an overall higher degree of improvement of the skin. These results support our understanding of the mechanisms behind the clinical efficacy observed for Cal/BD foam and of its use for long-term proactive treatment of psoriasis vulgaris.

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“…Particular mention should be made of steroid-induced atrophy as this is a common concern. Steroid-induced atrophy results from inhibition of cell proliferation and collagen synthesis (Table 1) [36,37]. This is dependent on the duration of use [38], potency [39], and anatomical area treated [2,40].…”

Section: Elephant Wrinklesmentioning

confidence: 99%

“…TCS use has been shown to result in barrier dysfunction [37,44,64]. In a hairless mouse model study, Lin et al [37] found that cessation of 0.064 % betamethasone dipropionate ointment after a 6-week use led to an increase in transepidermal water loss (TEWL), higher expression of Ki-67 (a cell proliferative marker) and upregulation of IL1-α, TNF-α and NF-κB. These cytokines gradually normalised after 1 week.…”

Section: Rebound Cytokine Cascade Secondary To Tcs Induced Barrier Impairmentmentioning

confidence: 99%

Steroid Phobia: Is There a Basis? A Review of Topical Steroid Safety, Addiction and Withdrawal

2021

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There is a growing concern amongst patients about topical corticosteroid (TCS) side effects, with increasing discussion of topical steroid addiction (TSA) and topical steroid withdrawal (TSW) particularly on social media platforms. However, the acceptance of TSA/TSW as a distinct condition remains controversial within the dermatological community. We conducted a literature search using PubMed, MEDLINE, Cochrane Library, Google Scholar, Embase and Web of Science to identify original articles addressing TSA/TSW. We described the definition and reported clinical features of TSA/TSW including its classification into erythemato-edematous and papulopustular subtype. To assess the validity of TSA/TSW, we summarised and objectively appraised the postulated mechanisms for this condition, including tachyphylaxis, dysregulation of glucocorticoid receptors, rebound vasodilation and impaired skin barrier leading to a cytokine cascade. Understanding the evidence including its limitations and uncertainties highlights areas for future research and helps medical practitioners better counsel and provide care to patients who may be experiencing or who have concerns about TSA/TSW.

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Barrier abnormalities and keratinocyte-derived cytokine cascade after cessation of long-term topical glucocorticosteroid on hairless mouse skin

Cited by 5 publications

References 39 publications

The Effect and Mechanism of Burnet Gels on Steroid-Dependent Dermatitis in Guinea Pig Model

The Effect and Mechanism of Burnet Gels on Steroid-Dependent Dermatitis in Guinea Pig Model

Calcipotriol/Betamethasone Dipropionate Foam Inhibits Th17 Cytokine Secretion and Improves Epidermal Barrier Markers in a Human Th17 Skin Inflammation Model

Steroid Phobia: Is There a Basis? A Review of Topical Steroid Safety, Addiction and Withdrawal

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