Janus Kinase Inhibitors Ameliorated Gastrointestinal Amyloidosis and Hypoalbuminemia in Persistent Dermatitis Mouse Model.
Janus Kinase Inhibitors Ameliorated Gastrointestinal Amyloidosis and Hypoalbuminemia in Persistent Dermatitis Mouse Model.
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DOI：
10.3390/ijms23010028
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发表时间：
2021-12-21
影响因子：
5.6
通讯作者：
Yamanaka K
中科院分区：
文献类型：
--
作者：
Nakanishi T;Mizutani K;Iida S;Matsushima Y;Umaoka A;Kondo M;Habe K;Yamanaka K
营养不良不仅被认为是类风湿性关节炎和炎症性肠病的并发症，也被认为是炎症性皮肤病的并发症;然而，其治疗机制和疗效尚未阐明。使用小鼠皮炎模型，我们研究了炎症性皮肤病中营养不良的病理生理学及其治疗效果。我们采用自发性皮肤炎症小鼠模型，在表皮角质形成细胞中过度表达人caspase-1。测量体重、营养水平和α1-抗胰蛋白酶粪便浓度。对胃肠道进行组织学和功能学研究。在空腹时强制喂食异硫氰酸黄绿素（FITC）-葡聚糖，并测量血浆FITC-葡聚糖。研究了抗肿瘤坏死因子-α（TNF-α）和白细胞介素（IL）-α/β抗体以及Janus激酶（JAK）抑制剂的治疗效果。与野生型同窝小鼠相比，炎症皮肤小鼠模型显示体重降低，血清白蛋白水平降低，胃、小肠和大肠中淀粉样蛋白沉积，α1-抗胰蛋白酶粪便浓度增加。然而，血浆FITC-葡聚糖在皮炎模型和野生型同窝仔之间没有变化。在皮炎模型的血浆中检测到肝脏中过度产生的血清淀粉样蛋白A1。抗TNF-α和IL-α/β抗体对淀粉样蛋白沉积有部分影响;然而，JAK抑制剂改善了胃肠道淀粉样变性，皮肤症状改善。慢性皮炎与胃肠道继发性淀粉样变性密切相关，导致低白蛋白血症。因此，积极控制皮肤炎症对于预防胃肠道并发症至关重要。
Malnutrition is not only regarded as a complication of rheumatoid arthritis and inflammatory bowel disease but also that of inflammatory skin disease; however, the mechanisms and efficacy of its treatment have not been elucidated. Using a mouse model of dermatitis, we investigated the pathophysiology of malnutrition in inflammatory skin conditions and efficacy of its treatment. We employed spontaneous skin inflammation mice models overexpressing human caspase-1 in the epidermal keratinocytes. Body weight, nutrition level, and α1-antitrypsin fecal concentration were measured. The gastrointestinal tract was histologically and functionally investigated. Fluorescein isothiocyanate (FITC)-dextran was forcibly fed on an empty stomach, and plasma FITC-dextran was measured. The treatment efficacy of antibodies against tumor necrosis factor-α (TNF-α) and interleukin (IL)-α/β as well as Janus kinase (JAK) inhibitors was investigated. Compared with wild-type littermates, the inflammatory skin mice models showed a lowered body weight, reduction of serum albumin level, amyloid deposition in the stomach, small intestine, and large intestine, and increased α1-antitrypsin fecal concentration. However, the plasma FITC-dextran was unchanged between the dermatitis models and wild-type littermates. The over-produced serum amyloid A1 in the liver was detected in the plasma in the dermatitis model. Antibodies against TNF-α and IL-α/β showed partial effects on amyloid deposition; however, JAK inhibitors improved gastrointestinal amyloidosis with the improvement of skin symptoms. Chronic dermatitis is closely related to secondary amyloidosis in the gastrointestinal tract, resulting in hypoalbuminemia. Therefore, active control of skin inflammation is essential for preventing gastrointestinal complications.
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影响因子：
5.6
作者：
Mizutani, Kento;Shirakami, Eri;Yamanaka, Keiichi
通讯作者：
Yamanaka, Keiichi
影响因子：
4.7
作者：
Umaoka A;Takeuchi H;Mizutani K;Seo N;Matsushima Y;Habe K;Hagimori K;Yamaguchi Y;Ikeda T;Yamanaka K
通讯作者：
Yamanaka K
影响因子：
3.7
作者：
Yamanaka K;Nakanishi T;Saito H;Maruyama J;Isoda K;Yokochi A;Imanaka-Yoshida K;Tsuda K;Kakeda M;Okamoto R;Fujita S;Iwakura Y;Suzuki N;Ito M;Maruyama K;Gabazza EC;Yoshida T;Shimaoka M;Mizutani H
通讯作者：
Mizutani H
影响因子：
4.4
作者：
Zhang, N;Ahsan, MH;West, DB
通讯作者：
West, DB
影响因子：
4.4
作者：
Yamanaka, K;Tanaka, M;Mizutani, H
通讯作者：
Mizutani, H