Mechanisms of IFN-γ–induced apoptosis of human skin keratinocytes in patients with atopic dermatitis

Rebane, Ana; Zimmermann, Maya; Aab, Alar; Baurecht, Hansjörg; Koreck, Andrea; Karelson, Maire; Abram, Kristi; Metsalu, Tauno; Pihlap, Maire; Meyer, Norbert; Fölster‐Holst, Regina; Nagy, Nikoletta; Kemény, Lajos; Kingo, Külli; Vilo, Jaak; Illig, Thomas; Akdiş, Mübeccel; Franke, André; Novak, Natalija; Weidinger, Stephan; Akdiş, Cezmi A.

doi:10.1016/j.jaci.2012.02.020

Cited by 137 publications

(91 citation statements)

References 41 publications

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“…Moreover, the IFN-γ reduction would lead to a decreased expression of other cytokines such as IL-31 and IL-33 [28] and to the improvement of clinical features such as spongiosis. In fact, IFN-γ is implicated in keratinocyte apoptosis, which leads to eczema and spongiosis in patients with AD [29]. …”

Section: Discussionmentioning

confidence: 99%

Vitamin D Supplementation Modulates the Immune System and Improves Atopic Dermatitis in Children

Filippo

Scaparrotta

Rapino

et al. 2015

Int Arch Allergy Immunol

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Background: Vitamin D seems to influence the evolution of atopic dermatitis (AD) in children. Methods: We tested the vitamin D serum levels of 39 children with AD (AD group t₀) and of 20 nonallergic healthy controls (C group). AD severity was evaluated using the AD scoring system (SCORAD index). Cytokine serum levels (IL-2, IL-4, IL-6, IFN-γ, TNF-α) and atopy biomarkers were also measured. The patients were then treated with vitamin D oral supplementation of 1,000 IU/day (25 mg/day) for 3 months. We then reevaluated the vitamin D serum levels, AD severity and cytokine serum levels in all of the treated children (AD group t₁). Results: The cross-sectional analysis on patients affected by AD (AD group t₀) showed that the initial levels of all the tested cytokines except for TNF-α were higher than those of the healthy control group (C group), falling outside the normal range. After 3 months of supplementation the patients had significantly increased vitamin D levels (from 22.97 ± 8.03 to 29.41 ± 10.73 ng/ml; p = 0.01). A concomitant significant reduction of both the SCORAD index (46.13 ± 15.68 at the first visit vs. 22.57 ± 15.28 at the second visit; p < 0.001) and of all the altered cytokines (IL-2, IL-4, IL-6, IFN-γ) was also found. Conclusions: This study showed vitamin D supplementation to be an effective treatment in reducing AD severity in children through normalization of the Th1 and Th2 interleukin serum pattern.

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Section: Discussionmentioning

confidence: 99%

Vitamin D Supplementation Modulates the Immune System and Improves Atopic Dermatitis in Children

Filippo

Scaparrotta

Rapino

et al. 2015

Int Arch Allergy Immunol

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“…Other cytokines, such as IP-10, TNF-α, and interleukin (IL)-18, are also synthesized by keratinocytes in affected tissues [32]. Interferon-γ induces the apoptosis of keratinocytes in patients with atopic dermatitis [33]. Moreover, TWEAK alone induces the apoptosis of keratinocytes originating from affected skin, which can be exaggerated by TNF-α [8].…”

Section: Inflammatory Microenvironments Influence the Effect Of Tweakmentioning

confidence: 99%

Tumor Necrosis Factor Receptor Mediates Fibroblast Growth Factor-Inducible 14 Signaling

Wang¹,

Xiao²,

Xia³

2017

Cell Physiol Biochem

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Tumor necrosis factor (TNF)-related weak inducer of apoptosis (TWEAK) engages its sole receptor, fibroblast growth factor–inducible 14 (Fn14), which participates in various inflammatory and immunologic processes. TWEAK/Fn14 interaction induces different cell fates depending on the local microenvironment, which correlates with certain expression profiles of TNF receptors (TNFR). The predominant expression of TNFR1 or TNFR2 facilitates cell death or proliferation, respectively, on TWEAK/Fn14 activation. TNFR-associated factors (TRAF) interact with Fn14, cellular inhibitor of apoptosis protein (cIAP)-1, and TNFR, consequently transducing signals from TWEAK to downstream cytokines and cell cycle mediators. An Fn14-TRAF2-TNFR axis has been suggested in the function of TWEAK/Fn14 signaling, which may serve as a target in the development of novel therapeutic strategies for many diseases that have Fn14-overexpressing cells in affected tissues. The aims of this review are: 1) to present the main results on TWEAK/Fn14 regulation of cell fates, 2) to analyze the mechanism of the Fn14-TRAF2-TNFR axis, and 3) to summarize the potential strategies in the pharmacologic targeting of this axis.

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“…Moreover, the IFN-γ reduction would lead to a decreased expression of other cytokines such as IL-31 and IL-33 and to the improvement of clinical features such as spongiosis [34]. In fact IFN-γ is implicated in keratinocyte apoptosis which leads to eczema and spongiosis in patients with AD [35].…”

Section: Groupmentioning

confidence: 99%

Estimation of Calcidiol Level in Serum of Atopic Dermatitis Patients before and after NB-UVB Phototherapy in Comparison to Oral Vitamin D Therapy

Youssef¹,

Dorgham²,

Hegazy³

et al. 2017

J Clin Exp Dermatol Res

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Mechanisms of IFN-γ–induced apoptosis of human skin keratinocytes in patients with atopic dermatitis

Cited by 137 publications

References 41 publications

Vitamin D Supplementation Modulates the Immune System and Improves Atopic Dermatitis in Children

Vitamin D Supplementation Modulates the Immune System and Improves Atopic Dermatitis in Children

Tumor Necrosis Factor Receptor Mediates Fibroblast Growth Factor-Inducible 14 Signaling

Estimation of Calcidiol Level in Serum of Atopic Dermatitis Patients before and after NB-UVB Phototherapy in Comparison to Oral Vitamin D Therapy

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