TWEAK mediates inflammation in experimental atopic dermatitis and psoriasis

Sidler, Daniel; Wu, Ping; Herro, Rana; Claus, Meike; Wolf, Dennis; Kawakami, Yuko; Kawakami, Toshiaki; Burkly, Linda C.; Croft, Michael

doi:10.1038/ncomms15395

Cited by 55 publications

(82 citation statements)

References 73 publications

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“…Moreover, subcutaneous injection of TWEAK into mice induces histological and inflammatory signs of atopic dermatitis [12]. TWEAK deficiency protects mice from atopic dermatitis-like disease induced by house dust mite allergen and staphylococcal enterotoxin B [12]. This study provided additional evidence that both TWEAK and Fn14 are more expressed in lesional skin of atopic dermatitis.…”

Section: Discussionmentioning

confidence: 71%

“…An important phenomenon was that IL‐17 is increased upon the stimulation of the cytokine cocktail of atopic dermatitis, TWEAK alone or their combination, while IFN‐γ and IL‐18 are exclusively affected by this cocktail or their combination. In fact, TWEAK directly induces the production of IL‐17 in keratinocytes . Thus, these cytokines mediate the function of TWEAK/Fn14 signals in the pathogenesis of atopic dermatitis.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies showed that TWEAK and Fn14 are up-regulated in skin lesions of patients with atopic dermatitis [10][11][12], although the serum level of TWEAK is not elevated [6,10,11]. Moreover, subcutaneous injection of TWEAK into mice induces histological and inflammatory signs of atopic dermatitis [12]. TWEAK deficiency protects mice from atopic dermatitis-like disease induced by house dust mite allergen and staphylococcal enterotoxin B [12].…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies showed that both TWEAK and Fn14 are highly expressed in the skin lesion of patients with eczema or atopic dermatitis [10][11][12]. Moreover, TWEAK deficiency limits the severity of atopic dermatitis in a murine model [12]. These findings strongly suggest that TWEAK/Fn14 activation participates in the development of atopic dermatitis.…”

Section: Introductionmentioning

confidence: 93%

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Experimental atopic dermatitis is dependent on the TWEAK/Fn14 signaling pathway

Liu¹,

Wang²,

Wang³

et al. 2019

Clinical and Experimental Immunology

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Summary Tumor necrosis factor (TNF)‐like weak inducer of apoptosis (TWEAK) acts through its receptor fibroblast growth factor inducible 14 (Fn14), and participates in skin inflammation. Both TWEAK and Fn14 are highly expressed in skin lesions of patients with atopic dermatitis. The purpose of this study was to further explore the effect of Fn14 inhibition on experimental atopic dermatitis. Experimental atopic dermatitis was induced in the wild‐type and Fn14 knock‐out BALB/c mice. The effect of TWEAK/Fn14 interaction on keratinocytes was studied in an in‐vitro model of atopic dermatitis. Fn14 deficiency ameliorates skin lesions in the mice model, accompanied by less infiltration of inflammatory cells and lower local levels of proinflammatory cytokines, including TWEAK, TNF‐α and interleukin (IL)‐17. Fn14 deficiency also attenuates the up‐regulation of TNFR1 in skin lesions of atopic dermatitis. Moreover, topical TWEAK exacerbates skin lesion in the wild‐type but not in the Fn14 knock‐out mice. In vitro, TWEAK enhances the expressions of IL‐17, IL‐18 and IFN‐γ in keratinocytes under atopic dermatitis‐like inflammation. These results suggest that Fn14 deficiency protects mice from experimental atopic dermatitis, involving the attenuation of inflammatory responses and keratinocyte apoptosis. In the context of atopic dermatitis‐like inflammation, TWEAK modulates keratinocytes via a TNFR1‐mediated pathway.

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Section: Discussionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 93%

See 2 more Smart Citations

Experimental atopic dermatitis is dependent on the TWEAK/Fn14 signaling pathway

Liu¹,

Wang²,

Wang³

et al. 2019

Clinical and Experimental Immunology

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“…Psoriasis is a debilitating chronic skin disease characterized by inflamed, sharply demarcated, erythematous plaques with epidermal hyperproliferation, hyperkeratosis, parakeratosis, dermal capillaries dilation, and infiltration of inflammatory cells (Krueger & Bowcock, ; Sidler et al, ). In psoriasis disease condition cytokines, chemokines, and growth factors are the culpable factors, which attributes to aberrant crosstalk between immune cells and keratinocytes, that reinforce the epidermal hyperplasia (Martin et al, ).…”

Section: Introductionmentioning

confidence: 99%

Repurposing an old drug for new use: Niclosamide in psoriasis‐like skin inflammation

Thatikonda

Pooladanda

Godugu

2019

Journal Cellular Physiology

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Drug discovery is an onerous, extremely expensive, and time‐consuming process. Instead, drug repurposing is an attractive strategy for exploiting novel indications for a drug beyond its original use. The untapped potential of drug repurposing compensates the barriers associated with the drug discovery pipeline. Psoriasis is an autoimmune skin disease, where hyperproliferation of keratinocytes and exaggerated immune responses are the important hallmarks of the disease. Extensive in vitro and preclinical research has demonstrated that niclosamide was found to exert potent anticancer and anti‐inflammatory properties by targeting STAT3, p65 NF‐κB, and NFATc‐1 signaling paradigm with minimal host toxicity. From the disease perspective, the static intracellular molecular network in both cancer and psoriasis share overlapping pathological features in terms of hyperproliferation and chronic inflammation, which is mediated by the aforementioned signaling cascade. The plausible mechanistic relevance has prompted us to investigate the implementation of niclosamide for repositioning in psoriasis. Our in vitro and in vivo findings suggest that niclosamide inhibits keratinocytes hyperproliferation by reactive oxygen species‐mediated apoptosis through the loss of mitochondrial membrane potential, cell cycle arrest at Sub G1 phase, and DNA fragmentation. Furthermore, niclosamide treatment resulted in abrogation of lipopolysaccharide‐induced inflammatory cytokine levels in murine macrophages. Additionally, our results provided a preclinical rationale in imiquimod (IMQ)‐induced BALB/c mouse model, where niclosamide diligently mitigated the IMQ‐induced epidermal hyperplasia and inflammation by downregulating STAT3, p65 NF‐κB, and NFATc‐1 transcription factors along with Akt, Ki‐67, and ICAM‐1 protein expression.

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Pre‐diagnostic plasma inflammatory proteins and risk of hepatocellular carcinoma in three population‐based cohort studies from the United States and the United Kingdom

Zhao,

Zhang,

Birmann

et al. 2024

Intl Journal of Cancer

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Previous studies suggest a role for inflammation in hepatocarcinogenesis. However, no study has comprehensively evaluated associations between circulating inflammatory proteins and risk of hepatocellular carcinoma (HCC) among the general population. We conducted a nested case–control study in the Nurses' Health Study (NHS) and the Health Professionals Follow‐up Study (HPFS) with 56 pairs of incident HCC cases and controls. External validation was performed in the UK Biobank (34 HCC cases and 48,471 non‐HCC controls). Inflammatory protein levels were measured in pre‐diagnostic plasma using the Olink® Inflammation Panel. We used conditional logistic regression to calculate multivariable odds ratios (ORs) with 95% confidence intervals (CIs) for associations between a 1‐standard deviation (SD) increase in biomarker levels and HCC risk, considering a statistically significant threshold of false discovery rate (FDR)‐adjusted p < .05. In the NHS/HPFS, among 70 analyzed proteins with call rates >80%, 15 proteins had significant associations with HCC risk (pFDR < .05). Two proteins (stem cell factor, OR per SD = 0.31, 95% CI = 0.16–0.58; tumor necrosis factor superfamily member 12, OR per SD = 0.51, 95% CI = 0.31–0.85) were inversely associated whereas 13 proteins were positively associated with risk of HCC; positive ORs per SD ranged from 1.73 for interleukin (IL)‐10 to 2.35 for C‐C motif chemokine‐19. A total of 11 proteins were further replicated in the UK Biobank. Seven of the eight selected positively associated proteins also showed positive associations with HCC risk by enzyme‐linked immunosorbent assay, with ORs ranging from 1.56 for IL‐10 to 2.72 for hepatocyte growth factor. More studies are warranted to further investigate the roles of these observed inflammatory proteins in HCC etiology, early detection, risk stratification, and disease treatment.

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TWEAK mediates inflammation in experimental atopic dermatitis and psoriasis

Cited by 55 publications

References 73 publications

Experimental atopic dermatitis is dependent on the TWEAK/Fn14 signaling pathway

Experimental atopic dermatitis is dependent on the TWEAK/Fn14 signaling pathway

Repurposing an old drug for new use: Niclosamide in psoriasis‐like skin inflammation

Pre‐diagnostic plasma inflammatory proteins and risk of hepatocellular carcinoma in three population‐based cohort studies from the United States and the United Kingdom

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