Aryl Hydrocarbon Receptor Role in Co-Ordinating SARS-CoV-2 Entry and Symptomatology: Linking Cytotoxicity Changes in COVID-19 and Cancers; Modulation by Racial Discrimination Stress.
Aryl Hydrocarbon Receptor Role in Co-Ordinating SARS-CoV-2 Entry and Symptomatology: Linking Cytotoxicity Changes in COVID-19 and Cancers; Modulation by Racial Discrimination Stress.
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DOI：
10.3390/biology9090249
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发表时间：
2020-08-27
期刊：
影响因子：
4.2
通讯作者：
Mazzoccoli G
中科院分区：
文献类型：
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作者：
Anderson G;Carbone A;Mazzoccoli G
芳香烃受体（AhR）在协调严重急性呼吸道综合征-冠状病毒-2（SARS-CoV-2）的进入和病理生理学方面的作用未得到充分认识，这是COVID-19大流行的基础。在“细胞因子风暴”期间促炎细胞因子的升高诱导吲哚胺2，3-双加氧酶（IDO），导致激活AhR的犬尿氨酸增加，从而提高初始促炎细胞因子阶段并抑制内源性抗病毒应答。这种AhR驱动的变化巩固了与先前存在的高风险医疗条件（如II型糖尿病）相关的严重程度和死亡率的提高，以及种族歧视压力如何导致来自亚洲黑人和少数民族（BAME）社区的人的严重程度/死亡率的提高。AhR在调节线粒体代谢和协调专门的促消退介质（SPM）、褪黑激素能途径、乙酰辅酶A和环氧合酶（考克斯）2-前列腺素（PG）E2途径中是关键的，其支持内源性抗病毒细胞中的“耗竭”，与在所有癌症中明显的溶细胞免疫细胞中的类似代谢抑制平行。促炎细胞因子诱导的肠道通透性/生态失调和松果体褪黑激素的抑制是AhR调节的更广泛的病理生理基础的方面。这对SARS-CoV-2感染和癌症的预防和治疗具有许多意义，未来的研究方向是更好地研究社会过程的生物学基础以及这些基础如何推动健康差距。
There is an under-recognized role of the aryl hydrocarbon receptor (AhR) in co-ordinating the entry and pathophysiology of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) that underpins the COVID-19 pandemic. The rise in pro-inflammatory cytokines during the ‘cytokine storm’ induce indoleamine 2,3-dioxygenase (IDO), leading to an increase in kynurenine that activates the AhR, thereby heightening the initial pro-inflammatory cytokine phase and suppressing the endogenous anti-viral response. Such AhR-driven changes underpin the heightened severity and fatality associated with pre-existent high-risk medical conditions, such as type II diabetes, as well as to how racial discrimination stress contributes to the raised severity/fatality in people from the Black Asian and Minority Ethnic (BAME) communities. The AhR is pivotal in modulating mitochondrial metabolism and co-ordinating specialized, pro-resolving mediators (SPMs), the melatonergic pathways, acetyl-coenzyme A, and the cyclooxygenase (COX) 2-prostaglandin (PG) E2 pathway that underpin ‘exhaustion’ in the endogenous anti-viral cells, paralleling similar metabolic suppression in cytolytic immune cells that is evident across all cancers. The pro-inflammatory cytokine induced gut permeability/dysbiosis and suppression of pineal melatonin are aspects of the wider pathophysiological underpinnings regulated by the AhR. This has a number of prophylactic and treatment implications for SARS-CoV-2 infection and cancers and future research directions that better investigate the biological underpinnings of social processes and how these may drive health disparities.
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DOI：
10.3390/ijerph17155573
发表时间：
2020-08-01
影响因子：
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作者：
Borro, Marina;Di Girolamo, Paolo;Simmaco, Maurizio
通讯作者：
Simmaco, Maurizio
影响因子：
7.6
作者：
Brody, Gene H.;Yu, Tianyi;Chen, Edith
通讯作者：
Chen, Edith
影响因子：
11.8
作者：
Bordoni, Veronica;Sacchi, Alessandra;Agrati, Chiara
通讯作者：
Agrati, Chiara
影响因子：
12.4
作者：
Agrati, Chiara;Sacchi, Alessandra;Ippolito, Giuseppe
通讯作者：
Ippolito, Giuseppe
影响因子：
--
作者：
Ademosun, Ayokunle O;Oboh, Ganiyu
通讯作者：
Oboh, Ganiyu