The cholinergic system in guttate psoriasis with special reference to mast cells

Radosa, Julia; Dyck, Wilhelm; Goerdt, Sergij; Kurzen, Hjalmar

doi:10.1111/j.1600-0625.2011.01283.x

Cited by 28 publications

(31 citation statements)

References 12 publications

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“…Therefore, these results beg the question: What signalling mechanism is activated by the manifestation of colitis that could induce these mast cells in the distally located skin? Of central importance to this question are the high levels of nicotinic and muscarinic AChR expression on the mast cell surface and the ability of these ligand‐activated receptors to induce degranulation of the cell . Excessive degranulation invariably leads to cellular dysfunction, indicating that the non‐neuronal cholinergic system (via increased plasma acetylcholine levels) may play a role in the phenotype observed in our DSS‐treated mouse mode.…”

Section: Discussionmentioning

confidence: 98%

Impairment of skin barrier function via cholinergic signal transduction in a dextran sulphate sodium‐induced colitis mouse model

Yokoyama

Hiramoto

Koyama

et al. 2015

Experimental Dermatology

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Dry skin has been clinically associated with visceral diseases, including liver disease, as well as for our previously reported small intestinal injury mouse model, which have abnormalities in skin barrier function. To clarify this disease-induced skin disruption, we used a dextran sulphate sodium (DSS)-induced colitis mouse model. Following treatment with DSS, damage to the colon and skin was monitored using histological and protein analysis methods as well as the detection of inflammatory mediators in the plasma. Notably, transepidermal water loss was higher, and skin hydration was lower in DSS-treated mice compared to controls. Tumor necrosis factor-alpha (TNF-α), interleukin 6 and NO2-/NO3- levels were also upregulated in the plasma, and a decrease in body weight and colon length was observed in DSS-treated mice. However, when administered TNF-α antibody or an iNOS inhibitor, no change in skin condition was observed, indicating that another signalling mechanism is utilized. Interestingly, the number of tryptase-expressing mast cells, known for their role in immune function via cholinergic signal transduction, was elevated. To evaluate the function of cholinergic signalling in this context, atropine (a muscarinic cholinoceptor antagonist) or hexamethonium (a nicotinic cholinergic ganglion-blocking agent) was administered to DSS-treated mice. Our data indicate that muscarinic acetylcholine receptors (mAChRs) are the primary receptors functioning in colon-to-skin signal transduction, as DSS-induced skin disruption was suppressed by atropine. Thus, skin disruption is likely associated with DSS-induced colitis, and the activation of mast cells via mAChRs is critical to this association.

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Section: Discussionmentioning

confidence: 98%

Impairment of skin barrier function via cholinergic signal transduction in a dextran sulphate sodium‐induced colitis mouse model

Yokoyama

Hiramoto

Koyama

et al. 2015

Experimental Dermatology

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“…Furthermore, increased numbers of activated mast cells are often observed in and around lesional psoriatic skin, and increasing evidence suggests that mast cells are functionally important key immunocytes in the pathogenesis of psoriasis (Carvalho, Nilsson & Harvima, 2010; Namazi, 2005; Radosa et al, 2011; Suttle et al, 2012; Toruniowa & Jablonska, 1988). Recently, we have shown that CB1 activation limits excessive mast cell activity and even inhibits mast cell maturation of resident, intracutaneous progenitors (Sugawara et al, 2012).…”

Section: Resultsmentioning

confidence: 99%

A novel control of human keratin expression: cannabinoid receptor 1-mediated signaling down-regulates the expression of keratins K6 and K16 in human keratinocytesin vitroandin situ

Ramot

Sugawara

Zákány

et al. 2013

PeerJ

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Cannabinoid receptors (CB) are expressed throughout human skin epithelium. CB1 activation inhibits human hair growth and decreases proliferation of epidermal keratinocytes. Since psoriasis is a chronic hyperproliferative, inflammatory skin disease, it is conceivable that the therapeutic modulation of CB signaling, which can inhibit both proliferation and inflammation, could win a place in future psoriasis management. Given that psoriasis is characterized by up-regulation of keratins K6 and K16, we have investigated whether CB1 stimulation modulates their expression in human epidermis. Treatment of organ-cultured human skin with the CB1-specific agonist, arachidonoyl-chloro-ethanolamide (ACEA), decreased K6 and K16 staining intensity in situ. At the gene and protein levels, ACEA also decreased K6 expression of cultured HaCaT keratinocytes, which show some similarities to psoriatic keratinocytes. These effects were partly antagonized by the CB1-specific antagonist, AM251. While CB1-mediated signaling also significantly inhibited human epidermal keratinocyte proliferation in situ, as shown by K6/Ki-67-double immunofluorescence, the inhibitory effect of ACEA on K6 expression in situ was independent of its anti-proliferative effect. Given recent appreciation of the role of K6 as a functionally important protein that regulates epithelial wound healing in mice, it is conceivable that the novel CB1-mediated regulation of keratin 6/16 revealed here also is relevant to wound healing. Taken together, our results suggest that cannabinoids and their receptors constitute a novel, clinically relevant control element of human K6 and K16 expression.

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“…3A). Mast cells have AChRs, and degranulation of mast cells is regulated by these receptors111213. Destruction of the skin barrier on day seven may have involved the degranulation of mast cells via cholinergic signals.…”

Section: Discussionmentioning

confidence: 99%

Influence of Repeated Senna Laxative Use on Skin Barrier Function in Mice

et al. 2017

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BackgroundSenna, one of the major stimulant laxatives, is widely used for treating constipation. Chronic senna use has been reported to be associated with colonic disorders such as melanosis coli and/or epithelial hyperplasia. However, there is no obvious information on the influence of chronic senna use on organs except for the intestine.ObjectiveTo clarify the influence of senna laxative use on skin barrier function by repeated senna administration.MethodsEight-week-old male hairless mice received senna (10 mg/kg/day) for 21 days. After administration, we evaluated transepidermal water loss (TEWL), and investigated the biomarkers in plasma and skin using protein analysis methods.ResultsFecal water content on day seven was significantly increased; however, on day 21, it was significantly decreased after repeated senna administration. In the senna-administered group, TEWL was significantly higher compared to the control on days seven and 21. Plasma acetylcholine concentration and NO2 −/NO3 − were increased on days seven and 21, respectively. In skin, tryptase-positive mast cells and inducible nitric oxide synthase (iNOS)-positive cells were increased on days seven and 21, respectively. The increase of TEWL on days seven and 21 was suppressed by the administration of atropine and N(G)-nitro-L-arginine methyl ester, respectively.ConclusionIt was suggested that diarrhea or constipation induced by repeated senna administration caused the impairment of skin barrier function. There is a possibility that this impaired skin barrier function occurred due to degranulation of mast cells via cholinergic signals or oxidative stress derived from iNOS.

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The cholinergic system in guttate psoriasis with special reference to mast cells

Cited by 28 publications

References 12 publications

Impairment of skin barrier function via cholinergic signal transduction in a dextran sulphate sodium‐induced colitis mouse model

Impairment of skin barrier function via cholinergic signal transduction in a dextran sulphate sodium‐induced colitis mouse model

A novel control of human keratin expression: cannabinoid receptor 1-mediated signaling down-regulates the expression of keratins K6 and K16 in human keratinocytesin vitroandin situ

Influence of Repeated Senna Laxative Use on Skin Barrier Function in Mice

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