Thromboxane A2 is Involved in Itch-associated Responses in Mice with Atopic Dermatitis-like Skin Lesions

Andoh, Tsugunobu; Yamamoto, Ai; Haza, Satomi; Yuhki, Koh Ichi; Ushikubi, Fumitaka; Narumiya, Shuh; Kuraishi, Yasushi

doi:10.2340/00015555-2437

Cited by 10 publications

(9 citation statements)

References 39 publications

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“…Interestingly, the reduction on skin DHA and EPA has been associated with alteration in the epidermal barrier [13] , the decrease in PD1, PGF 1 , KETE and EET with inflammation [3] , [14] , [15] , TXB 2 indicating lesions [15] and 12-HHT through BLT2 receptor, has been described as a pro regenerative lipid mediator [16] . On the other hand, the local increase of PGD 2 , PGE 2, and HODEs has been associated with hair loss, inflammation and oxidative stress [17] , [18] , [19] .…”

Section: Discussionmentioning

confidence: 99%

The streptozotocin-high fat diet induced diabetic mouse model exhibits severe skin damage and alterations in local lipid mediators

2018

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BackgroundType 2 diabetes (T2D) can go undiagnosed for years, leading to a stage where produces complications such as delayed skin wound healing. Animal models have been developed in the last decades to study the pathological progression in this disease. Streptozotocin (STZ), that has a selective pharmacological toxicity toward pancreatic β cells, in addition to high fat diet has been widely used to induce diabetes however no evidence has shown its effects on the skin integrity.MethodsEighteen C57BL/6J male mice, were divided in 3 groups; the first was fed with chow diet and the second was kept on a high fat diet and the third injected with STZ intraperitoneal for 5 days consecutively before starting the diet protocol with high fat. Mice were maintained 5 weeks in total.ResultsWe show that animals treated with STZ-high fat diet exhibit skin injuries without significant alterations on basal insulin and triglycerides, compared to the control. The skin from these animals presents higher levels of oxidative stress, lower levels of adhesion proteins and alterations in lipid mediators, effects that are not produced by the high fat diet itself.ConclusionOur results suggest that this in vivo model represents a relevant approach for studying skin damage induced by diabetes.

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Section: Discussionmentioning

confidence: 99%

The streptozotocin-high fat diet induced diabetic mouse model exhibits severe skin damage and alterations in local lipid mediators

2018

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“…12 Furthermore, TXA 2 produced from epidermal keratinocytes is involved in spontaneous scratching in mice with dermatitis. 16 In this study, a-MSHeinduced scratching was inhibited by a TP receptor antagonist. Therefore, it is suggested that TXA 2 plays an important role in a-MSHemediated scratching in mice with dermatitis.…”

Section: Discussionmentioning

confidence: 67%

“…24 TP receptors are expressed in primary afferent neurons, and the activation of TP receptors increases the concentration of intracellular Ca 2þ ions. 12,16 Therefore, TXA 2 produced from a-MSHe stimulated keratinocytes directly acts on primary afferent neurons and elicits scratching. The DRG is an accumulation of cell bodies of primary afferent neurons.…”

Section: Discussionmentioning

confidence: 99%

“…In mice with dermatitis, it has been reported that TXA 2 released from epidermal keratinocytes can induce scratching. 16 Because a-MSH and its receptors (MC1R and MC5R) were expressed in epidermal keratinocytes, the inhibitory effect of TP receptor antagonist ONO-3708 was demonstrated for a-MSHeinduced scratching. ONO-3708 (100 mg/kg) significantly suppressed a-MSHeinduced scratching compared with vehicle for ONO-3708 (Figure 4C).…”

Section: Scratching Induced By A-msh In Healthy Mice and Effects Of Txa 2 Receptor (Tp Receptor) Antagonist On Behaviormentioning

confidence: 99%

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Involvement of α-Melanocyte–Stimulating Hormone–Thromboxane A2 System on Itching in Atopic Dermatitis

Andoh

Akasaka

Shimizu

et al. 2019

The American Journal of Pathology

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a-Melanocyteestimulating hormone (a-MSH) is an endogenous peptide hormone involved in cutaneous pigmentation in atopic dermatitis (AD) with severe itching. a-MSH elicits itch-related responses in mice. We, therefore, investigated whether a-MSH was involved in itching in AD. In the skin of AD patients and mice with atopy-like dermatitis, a-MSH and the prohormone convertase 2, which is the key processing enzyme for the production of a-MSH, were distributed mainly in keratinocytes. In the skin of mice with dermatitis, melanocortin receptors (MC1R and MC5R) were expressed at the mRNA level and were distributed in the dermis. In the dorsal root ganglion of mice with dermatitis, mRNAs encoding MC1R, MC3R, and MC5R were also expressed. MC1R antagonist agouti-signaling protein inhibited spontaneous scratching in mice with dermatitis. In healthy mice, intradermal a-MSH elicited itch-associated responses, which were inhibited by thromboxane (TX) A 2 receptor antagonist ONO-3708. In mouse keratinocytes, a-MSH increased the production of TXA 2 , which was inhibited by adenylyl cyclase inhibitor SQ-22536 and Ca 2þ chelator EGTA. In mouse keratinocytes treated with siRNA for MC1R and/or MC5R, a-MSHeinduced TXA 2 production was decreased. a-MSH increased intracellular Ca 2þ ion concentration in dorsal root ganglion neurons and keratinocytes. These results suggest that a-MSH is involved in itching during AD and may elicit itching through the direct action of primary afferents and TXA 2 production by keratinocytes.

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“…Other data suggest that PAR2 may perpetuate inflammatory pain and promote inflammation through a neurogenic mechanism . PAR2 pain and itch pathways seem to be mediated by the TRP channels and upregulated pruritogens such as thromboxane A2, leukotriene B4 and prostaglandin E2 …”

Section: Introductionmentioning

confidence: 99%

Update on protease‐activated receptor 2 in cutaneous barrier, differentiation, tumorigenesis and pigmentation, and its role in related dermatologic diseases

Henehan

Benedetto

2019

Experimental Dermatology

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Protease‐activated receptor 2 (PAR2) is a transmembrane receptor expressed by multiple tissues, including skin, with rapidly expanding knowledge regarding its roles. In the skin, PAR2 has extensively documented effects in promoting Th2 inflammation and pruritus; and its role in atopic dermatitis continues to be thoroughly studied. Numerous new investigations have shown a more complex range of activities potentially related to dermatologic diseases. Goal of this review is to outline emerging effects of PAR2 activation in the skin other than those related to immunologic and pruritic functions. Specifically, this work seeks to summarize current knowledge (and gaps) of PAR2 as a regulator of epidermal barrier, keratinocyte differentiation, cutaneous tumorigenesis and pigmentation. Additional focus will be placed on possible involvement in dermatologic disease and emergence as a therapeutic target.

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Thromboxane A2 is Involved in Itch-associated Responses in Mice with Atopic Dermatitis-like Skin Lesions

Cited by 10 publications

References 39 publications

The streptozotocin-high fat diet induced diabetic mouse model exhibits severe skin damage and alterations in local lipid mediators

The streptozotocin-high fat diet induced diabetic mouse model exhibits severe skin damage and alterations in local lipid mediators

Involvement of α-Melanocyte–Stimulating Hormone–Thromboxane A2 System on Itching in Atopic Dermatitis

Update on protease‐activated receptor 2 in cutaneous barrier, differentiation, tumorigenesis and pigmentation, and its role in related dermatologic diseases

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