Increased ZAP70 Is Involved in Dry Skin Pruritus in Aged Mice

Zhao, Nan; Gu, Min; Yang, Wenxiu; Zhang, Man; Tian, Qi; Ru, Liyan; Lü, Yang; Yu, Weihua

doi:10.1155/2016/6029538

Cited by 9 publications

(6 citation statements)

References 28 publications

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“…Thus, NLRP1 inflammasome may contribute to age-related chronic itch. Consistent with previous reports [64], we found that elderly mice exhibited more remarkable scratching behavior than young mice. Interestingly, the expression of NLRP1 inflammasome complexes and the related inflammatory cytokines is higher in elderly mice than in young mice.…”

Section: Discussionsupporting

confidence: 93%

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Spinal cord NLRP1 inflammasome contributes to dry skin induced chronic itch in mice

Fan

Gao

Song

et al. 2020

J Neuroinflammation

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Background: Dry skin itch is one of the most common skin diseases and elderly people are believed to be particularly prone to it. The inflammasome has been suggested to play an important role in chronic inflammatory disorders including inflammatory skin diseases such as psoriasis. However, little is known about the role of NLRP1 inflammasome in dry skin-induced chronic itch. Methods: Dry skin-induced chronic itch model was established by acetone-ether-water (AEW) treatment. Spontaneous scratching behavior was recorded by video monitoring. The expression of nucleotide oligomerization domain (NOD)-like receptor protein 1 (NLRP1) inflammasome complexes, transient receptor potential vanilloid type 1 (TRPV1), and the level of inflammatory cytokines were determined by western blot, quantitative real-time PCR, and enzyme-linked immunosorbent assay (ELISA) kits. Nlrp1a knockdown was performed by an adeno-associated virus (AAV) vector containing Nlrp1a-shRNA-eGFP infusion. H.E. staining was used to evaluate skin lesion. Results: AEW treatment triggers spontaneous scratching and significantly increases the expression of NLRP1, ASC, and caspase-1 and the levels of IL-1β, IL-18, IL-6, and TNF-α in the spinal cord and the skin of mice. Spinal cord Nlrp1a knockdown prevents AEW-induced NLRP1 inflammasome assembly, TRPV1 channel activation, and spontaneous scratching behavior. Capsazepine, a specific antagonist of TRPV1, can also inhibit AEW-induced inflammatory response and scratching behavior. Furthermore, elderly mice and female mice exhibited more significant AEW-induced scratching behavior than young mice and male mice, respectively. Interestingly, AEW-induced increases in the expression of NLRP1 inflammasome complex and the levels of inflammatory cytokines were more remarkable in elderly mice and female mice than in young mice and male mice, respectively. Conclusions: Spinal cord NLRP1 inflammasome-mediated inflammatory response contributes to dry skin-induced chronic itch by TRPV1 channel, and it is also involved in age and sex differences of chronic itch. Inhibition of NLRP1 inflammasome may offer a new therapy for dry skin itch.

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Section: Discussionsupporting

confidence: 93%

“…Aging results in impaired skin barrier function, immunosenescence, and neuropathic changes, which led to skin inflammation and pruritus [62,63]. Also, dry skin itch in elderly mice was more serious than in young mice [64]. However, little is known how age relates to chronic itch.…”

Section: Discussionmentioning

confidence: 99%

Spinal cord NLRP1 inflammasome contributes to dry skin induced chronic itch in mice

Fan

Gao

Song

et al. 2020

J Neuroinflammation

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“…ZAP70 expression was significantly increased, in addition to the secretion of IL-2 and NGF in 22-month-old AEW mice compared with 5-month-old AEW mice. This study revealed that increased ZAP70 is involved in dry skin in pruritus in elderly people, probably due to increased secretion of IL-2 and NGF ( 80 ).…”

Section: Mechanisms Of Itch In Dry Skinmentioning

confidence: 88%

Mechanisms and Management of Itch in Dry Skin

Moniaga¹,

Tominaga²,

Takamori³

2020

Acta Derm Venerol

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Itch is an unpleasant sensation that may disturb quality of life, and for which the pathomechanism and appropriate treatments are unclear. Chronic itch, which lasts more than 6 weeks, often accompanies pathological dry skin-based conditions, such as xerosis, atopic dermatitis, liver and kidney diseases. A decline in skin barrier function is thought to be the primary cause of itch induced by dry skin. Many kinds of mediators, receptors, and channels are involved in itch signalling among the skin nervous system, skin cells, and central nervous system. Several therapeutic options for itching have thus been developed, such as phototherapy, phospholipids, antioxidants, and emollients. Chronic itch is a burdensome clinical problem that often accompanies pathological dry skin-based conditions, such as atopic dermatitis, and systemic disorders, such as kidney diseases, with an unclear pathomechanism and treatments. One of the basic mouse models to investigate mechanisms of itch associated with dry skin is a mixture of acetone and ether followed by water. Animal studies using the acetone and ether followed by water model have revealed that many mediators and receptors, e.g. mas-related G protein-coupled receptor family, transient receptor potential, and chemokines, are responsible for itch and its hypersensitivity, supporting the hypothesis that dry skin-induced itch is a histamine-independent pathway. New insights have been acquired into the interplay between neurones and non-neuronal cells in the initiation, modulation, and sensitization of itch. Several thera peutic options for itching have thus been developed. This review summarizes the updated pathogenesis and therapeutic strategies for itch in dry skin conditions.

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“…Zeta-chain-associated protein kinase 70 (ZAP70), as a T-cell receptor, may induce interleukin 2 (IL-2) secretion and promote nerve growth factor (NGF) secretion in skin. Another study showed that increased ZAP70 is involved in dry skin in elderly pruritus, while increased secretion of IL-2 and NGF may induce dry-skin itching 27 . Dry skin is one of the major causes of itching.…”

Section: Discussionmentioning

confidence: 99%

Itching and its related factors in subtypes of eczema: a cross-sectional multicenter study in tertiary hospitals of China

Wang

Shi

et al. 2018

Sci Rep

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Itching is a leading symptom of eczema or dermatitis and has a great impact on patients’ lives. Previous studies on itching have focused mostly on atopic dermatitis (AD). A cross-sectional multicenter study was conducted among outpatients with eczema from 39 tertiary hospitals in mainland China from July 1 to September 30, 2014. This work elaborates on itching in different types of eczema. Itching was very common (97%, 8499/8758) in outpatients with eczema. The severity of the itch increased with age and disease duration (P < 0.001). The top three subtypes of dermatitis with severe itching were atopic dermatitis (30.4%), widespread eczema (30.1%), and asteatotic eczema (27.9%). Widespread eczema refers to the involvement of more than three body parts, without clinical features of other specific types of eczema. The proportion of outpatients without itching was highest in hand eczema (6.8%). Positive correlations were observed between the severity of itching and the proportions of different diseases based on trend tests, including atopic dermatitis (P < 0.001), widespread eczema (P < 0.001), asteatotic eczema (P < 0.001), and autosensitization dermatitis (P < 0.001). Eczema outpatients with older age, longer disease duration, and, especially, a history of allergic diseases might be more prone to itching.

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Increased ZAP70 Is Involved in Dry Skin Pruritus in Aged Mice

Cited by 9 publications

References 28 publications

Spinal cord NLRP1 inflammasome contributes to dry skin induced chronic itch in mice

Spinal cord NLRP1 inflammasome contributes to dry skin induced chronic itch in mice

Mechanisms and Management of Itch in Dry Skin

Itching and its related factors in subtypes of eczema: a cross-sectional multicenter study in tertiary hospitals of China

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