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Vol. 26, Art. 9 (pp. 211-256)    |    2025       

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The role of zinc in a20/nf-κb signaling (Review article)

Laletin V.S.

Irkutsk State Medical University of the Ministry of Health of Russia,
664003, Russian Federation, Irkutsk, st. Krasnogo vosstaniya 1
St. Petersburg State Pediatric Medical University, 194100, Russian Federation, St. Petersburg, Litovskaya str., 2

Brief summary

Zinc is involved in regulation of inflammation. Anti-inflammatory effects of zinc are associated with inhibition of transcription factor NF-κB, one of the key regulators of inflammation. Activation of NF-κB signaling pathway is followed by induction of A20 (TNFAIP3), a critical negative regulator of NF-κB. The mechanisms of NF-κB inhibition by A20 are mediated by its ubiquitin-editig functions. A20 is possibly the main target for zinc ions in regulation of NF-κB signaling pathway. Zinc is involved in A20 functioning both as a structural component and a regulator of A20 expression. Clinical studies of haploinsufficiency A20 and animal models with targeted inactivating mutations demonstrated that A20 ZnF-domain with its seven zinc fingers plays a critical role in regulation of inflammatory responses. The exact mechanisms of zinc-mediated induction of A20 are still unknown. Experimental cell line and animal studies revealed that zinc ions induce A20 expression by activation of zinc-sensing receptor GPR39 and by epigenetic modifications. A20 is involved in pathogenesis of chronic and acute inflammatory, autoimmune, cardiovascular and oncological diseases. The role of zinc in regulation and functioning of A20 and the importance of A20 as a therapeutic target allow to determine directions of further investigations of zinc therapeutic potential in the treatment of a variety of diseases.


Key words

zinc; inflammation; anti-inflammatory action; proinflammatory cytokines; polyubiquitin; haploinsufficiency A20; chronic inflammatory diseases; autoimmune diseases; cardiovascular diseases; oncological diseases

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