摘要
磷酸二酯酶(PDE)4是催化环腺苷3'',5''-单磷酸(cAMP),多种基因和蛋白质的细胞内第二信使和调节物的水解酶的超家族。细胞内cAMP的水平升高导致基因的激活,但也导致参与促炎反应的核因子-κB的抑制。通过增加cAMP水平,PDE4抑制剂如去甲肾上腺素减少促炎症TNFα,IFNγ和IL-17的产生,并增加脂多糖刺激的外周血单个核细胞中抗炎IL-10的产生,并且在牛皮癣患者中关节炎(PsA)。在PDE4抑制剂中,apremilast,roflumilast和crisabolore已被批准用于治疗牛皮癣和PsA,慢性阻塞性肺病和特应性皮炎。在牛皮癣和PsA的初步研究中,我们显示6个月时apremilast降低IFNγ+ CD3 + Th1细胞和IL-17 + CD3 + Th17细胞,增加调节性B细胞和调节性T细胞。在这次审查中,我们强调PDE4抑制剂在特应性皮炎,斑秃,葡萄膜炎,类风湿性关节炎,牛皮癣和PsA,系统性红斑狼疮,血管炎,系统性硬化,多发性硬化和炎性肠病中的最新发现。鉴于cAMP作为第二信使在不同细胞内途径中的作用,选择性PDE4抑制剂可能是各种免疫介导的疾病的治疗剂。
关键词: 自由抗原,自身免疫,婴儿,cAMP,脊髓灰质炎,牛皮癣关节炎,牛皮癣。
Current Medicinal Chemistry
Title:Phosphodiesterase 4 Inhibitors in Immune-mediated Diseases: Mode of Action, Clinical Applications, Current and Future Perspectives
Volume: 24 Issue: 28
关键词: 自由抗原,自身免疫,婴儿,cAMP,脊髓灰质炎,牛皮癣关节炎,牛皮癣。
摘要: Phosphodiesterase (PDE) 4 is a superfamily of enzymes that catalyze the hydrolysis of cyclic adenosine 3',5'-monophosphate (cAMP), an intracellular second messenger and regulator of a wide array of genes and proteins. Increased levels of intracellular cAMP lead to activation of genes but also to inhibition of nuclear factor-kappa B, involved in pro-inflammatory responses. By increasing cAMP levels, PDE4 inhibitors, such as apremilast, reduced production of pro-inflammatory TNFα, IFNγ, and IL-17 and increased production of anti-inflammatory IL-10 in lipopolysaccharide-stimulated peripheral blood mononuclear cells, and in patients with psoriatic arthritis (PsA). Among PDE4 inhibitors, apremilast, roflumilast, and crisabolore have been approved for the treatment of psoriasis and PsA, chronic obstructive pulmonary disease, and atopic dermatitis, respectively. In a preliminary study on psoriasis and PsA we showed that at 6 months apremilast decreased IFNγ+CD3+ Th1 cells and IL- 17+CD3+ Th17 cells and increased regulatory B cells and regulatory T cells. In this review, we highlight recent findings of PDE4 inhibitors in atopic dermatitis, alopecia areata, uveitis, rheumatoid arthritis, psoriasis and PsA, systemic lupus erythematosus, vasculitis, systemic sclerosis, multiple sclerosis and inflammatory bowel disease. Given the role of cAMP as second messenger in diverse intracellular pathways, selective PDE4 inhibitors are likely to be therapeutic agents for various immune mediated diseases.
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Cite this article as:
Phosphodiesterase 4 Inhibitors in Immune-mediated Diseases: Mode of Action, Clinical Applications, Current and Future Perspectives, Current Medicinal Chemistry 2017; 24 (28) . https://dx.doi.org/10.2174/0929867324666170530093902
DOI https://dx.doi.org/10.2174/0929867324666170530093902 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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