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

Abstract

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.

Adverse Reaction of Dextran Sodium Sulfate-Induced Colitis in a Collagen-Induced Mouse Arthritis Model

“…Previously, we separately described various biological factors associated with rheumatoid arthritis and ulcerative colitis by using a mouse rheumatoid arthritis model and a dextran sodium sulfate (DSS)-induced colitis model in mice, respectively. [6][7][8][9] In the current study, we examined DSS-induced colitis in conjunction with the rheumatoid arthritis model in mice and confirmed deterioration factors of each condition with an aim of revealing the relationship between rheumatoid arthritis and ulcerative colitis.…”

“…10) Measurement of Hind Foot Volume As a reflection of the level of edema, the hind foot volume of each mouse was measured on the final experimental day using the method described in our previous report. 6,7) Briefly, in the beaker filled with distilled water, the hind foot of each group mice was immersed to the joints, and the hind foot volume was measured.…”

Ameliorative Effect of Hochu-ekki-to on Natural Skin Aging

“…Transepidermal water loss (TEWL) and skin hydration levels in the dorsal skin were measured at 2 years after starting the experiment by using a previously described method [16]. Briefly, TEWL, a permeability measurement that reflected the barrier function of the skin, was determined using a Tewameter TM300 (Courage + Khazaka Electronic GmbH, Cologne, Germany).…”

Ameliorative Effect of High-Dose Vitamin C Administration on Dextran Sulfate Sodium-Induced Colitis Mouse Model

“…19) Additionally, it was reported that highdose vitamin C administration has anticancer effects. [20][21][22] Our previous analyses indicated that high doses of vitamin C was significantly effective against colorectal cancer (unpublished). However, the effects of high-dose vitamin C therapy on ulcerative colitis are unknown.…”