CYP1A1 Enzymatic Activity Influences Skin Inflammation Via Regulation of the AHR Pathway.
CYP1A1 Enzymatic Activity Influences Skin Inflammation Via Regulation of the AHR Pathway.
复制标题
CYP1A1酶活性通过调节AHR途径影响皮肤炎症。
DOI：
10.1016/j.jid.2020.11.024
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发表时间：
2021-06
期刊：
影响因子：
--
通讯作者：
Di Meglio P
中科院分区：
文献类型：
--
作者：
Kyoreva M;Li Y;Hoosenally M;Hardman-Smart J;Morrison K;Tosi I;Tolaini M;Barinaga G;Stockinger B;Mrowietz U;Nestle FO;Smith CH;Barker JN;Di Meglio P
AHR是一种由各种人造和天然配体激活的环境传感器和转录因子，其最近已成为屏障器官如皮肤的稳态的关键调节剂。AHR通路的激活下调了动物模型和银屑病临床样本中的皮肤炎症反应。在这项研究中，我们确定CYP 1A 1酶活性作为皮肤炎症背景下有益AHR信号传导的关键调节因子。组成型表达Cyp 1a 1的小鼠在皮肤中表现出增加的CYP 1A 1酶活性，这导致免疫细胞活化和皮肤病理学加剧，反映了在Ahr缺陷小鼠中观察到的情况。抑制CYP 1A 1酶活性通过恢复有益的AHR信号传导改善皮肤免疫病理学。重要的是，与健康供体相比，银屑病患者显示AHR途径活化减少和CYP 1A 1酶活性增加，表明AHR/CYP 1A 1轴失调可能在炎症性皮肤病中起作用。因此，CYP 1A 1活性的调节可能代表了一种有前途的替代策略，以利用皮肤中AHR通路激活所产生的抗炎作用。
The AHR is an environmental sensor and transcription factor activated by a variety of man-made and natural ligands, which has recently emerged as a critical regulator of homeostasis at barrier organs such as the skin. Activation of the AHR pathway downmodulates skin inflammatory responses in animal models and psoriasis clinical samples. In this study, we identify CYP1A1 enzymatic activity as a critical regulator of beneficial AHR signaling in the context of skin inflammation. Mice constitutively expressing Cyp1a1 displayed increased CYP1A1 enzymatic activity in the skin, which resulted in exacerbated immune cell activation and skin pathology, mirroring that observed in Ahr-deficient mice. Inhibition of CYP1A1 enzymatic activity ameliorated the skin immunopathology by restoring beneficial AHR signaling. Importantly, patients with psoriasis displayed reduced activation of the AHR pathway and increased CYP1A1 enzymatic activity compared with healthy donors, suggesting that dysregulation of the AHR/CYP1A1 axis may play a role in inflammatory skin disease. Thus, modulation of CYP1A1 activity may represent a promising alternative strategy to harness the anti-inflammatory effect exerted by activation of the AHR pathway in the skin.
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影响因子：
5.5
作者：
Mulero-Navarro S;Fernandez-Salguero PM
通讯作者：
Fernandez-Salguero PM
DOI：
10.2147/ptt.s85189
发表时间：
2016
期刊：
Psoriasis (Auckland, N.Z.)
影响因子：
--
作者：
Naldi L
通讯作者：
Naldi L
影响因子：
16.8
作者：
Shinde R;McGaha TL
通讯作者：
McGaha TL
影响因子：
82.9
作者：
Rothhammer V;Mascanfroni ID;Bunse L;Takenaka MC;Kenison JE;Mayo L;Chao CC;Patel B;Yan R;Blain M;Alvarez JI;Kébir H;Anandasabapathy N;Izquierdo G;Jung S;Obholzer N;Pochet N;Clish CB;Prinz M;Prat A;Antel J;Quintana FJ
通讯作者：
Quintana FJ
影响因子：
--
作者：
Santes-Palacios R;Ornelas-Ayala D;Cabañas N;Marroquín-Pérez A;Hernández-Magaña A;Del Rosario Olguín-Reyes S;Camacho-Carranza R;Espinosa-Aguirre JJ
通讯作者：
Espinosa-Aguirre JJ