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25.04.2023

Disruption of the ADAM17/NF-κB feedback loop in astrocytes ameliorates HIV-1 Tat-induced inflammatory response and neuronal death

verfasst von: Xiaoxia Qiu, Jianjun Wang, Wei Zhang, Chengwei Duan, Tianpeng Chen, Dongmei Zhang, Jianbin Su, Lin Gao

Erschienen in: Journal of NeuroVirology | Ausgabe 3/2023

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Abstract

A disintegrin and metalloproteinases (ADAMs) are involved in multiple neurodegenerative diseases. However, the roles and mechanisms of ADAMs in HIV-associated neurocognitive disorder (HAND) remain unclear. Transactivator of transcription (Tat) induces inflammatory response in astrocytes, thereby leading to neuronal apoptosis in the central nervous system. In this study, we determined that ADAM17 expression was upregulated during soluble Tat stimulus in HEB astroglial cells. Inhibition of ADAM17 suppressed Tat-induced pro-inflammatory cytokines production and rescued the astrocytes-derived conditioned media (ACM)-mediated SH-SY5Y neural cells apoptosis. Moreover, ADAM17 mediated Tat-triggered inflammatory response in a NF-κB-dependent manner. Conversely, Tat induced ADAM17 expression via NF-κB signaling pathway. In addition, pharmacological inhibition of NF-κB signaling inhibited Tat-induced inflammatory response, which could be rescued by overexpression of ADAM17. Taken together, our study clarifies the potential role of the ADAM17/NF-κB feedback loop in Tat-induced inflammatory response in astrocytes and the ACM-mediated neuronal death, which could be a novel therapeutic target for relief of HAND.

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Titel: Disruption of the ADAM17/NF-κB feedback loop in astrocytes ameliorates HIV-1 Tat-induced inflammatory response and neuronal death
verfasst von: Xiaoxia Qiu
Jianjun Wang
Wei Zhang
Chengwei Duan
Tianpeng Chen
Dongmei Zhang
Jianbin Su
Lin Gao
Publikationsdatum: 25.04.2023
Verlag: Springer International Publishing
Erschienen in: Journal of NeuroVirology / Ausgabe 3/2023
Print ISSN: 1355-0284
Elektronische ISSN: 1538-2443
DOI: https://doi.org/10.1007/s13365-023-01131-5

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Disruption of the ADAM17/NF-κB feedback loop in astrocytes ameliorates HIV-1 Tat-induced inflammatory response and neuronal death

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