Metallothionein-3-mediated intracellular zinc mediates antioxidant and anti-inflammatory responses in the complete Freund’s adjuvant-induced inflammatory pain mouse model

Abstract Chronic inflammatory pain is often caused by peripheral tissue damage and persistent inflammation. This disease substantially affects patients’ physical and social well-being. We investigated the role of metallothionein-3 (MT3) in modulating complete Freund’s adjuvant (CFA)-induced intracel...

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Main Authors: Ngoc Buu Tran, Sook-Jeong Lee
Format: Article
Language:English
Published: Nature Publishing Group 2025-02-01
Series:Cell Death Discovery
Online Access:https://doi.org/10.1038/s41420-025-02322-1
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author Ngoc Buu Tran
Sook-Jeong Lee
author_facet Ngoc Buu Tran
Sook-Jeong Lee
author_sort Ngoc Buu Tran
collection DOAJ
description Abstract Chronic inflammatory pain is often caused by peripheral tissue damage and persistent inflammation. This disease substantially affects patients’ physical and social well-being. We investigated the role of metallothionein-3 (MT3) in modulating complete Freund’s adjuvant (CFA)-induced intracellular Zn2+ activity in an MT3 knockout mouse model of inflammatory pain in the hind paw. The results demonstrated that increasing intracellular Zn2+ levels ameliorate deficits in motor behavior, as well as inflammation in the paw, spleen, and thymus. Furthermore, intracellular Zn2+ was crucial in regulating oxidative stress markers (glutathione, superoxide dismutase, catalase, and malondialdehyde) and inflammatory cytokines, such as tumor necrosis factor-α and interleukin-6, in MT3 knockout mice induced with CFA. This study highlights the critical role of MT3 in coordinating the intracellular interaction with Zn2+, which is vital for the immune systems’s protective functions. These interactions are fundamental for maintaining metal ion homeostasis and regulating the synthesis of various biomolecules in the body.
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spelling doaj-art-c6d7179db785445e861ad9ec6a98991c2025-02-09T12:12:30ZengNature Publishing GroupCell Death Discovery2058-77162025-02-0111111110.1038/s41420-025-02322-1Metallothionein-3-mediated intracellular zinc mediates antioxidant and anti-inflammatory responses in the complete Freund’s adjuvant-induced inflammatory pain mouse modelNgoc Buu Tran0Sook-Jeong Lee1Department of Bioactive Material Sciences and Research Center of Bioactive Materials, Jeonbuk National UniversityDepartment of Bioactive Material Sciences and Research Center of Bioactive Materials, Jeonbuk National UniversityAbstract Chronic inflammatory pain is often caused by peripheral tissue damage and persistent inflammation. This disease substantially affects patients’ physical and social well-being. We investigated the role of metallothionein-3 (MT3) in modulating complete Freund’s adjuvant (CFA)-induced intracellular Zn2+ activity in an MT3 knockout mouse model of inflammatory pain in the hind paw. The results demonstrated that increasing intracellular Zn2+ levels ameliorate deficits in motor behavior, as well as inflammation in the paw, spleen, and thymus. Furthermore, intracellular Zn2+ was crucial in regulating oxidative stress markers (glutathione, superoxide dismutase, catalase, and malondialdehyde) and inflammatory cytokines, such as tumor necrosis factor-α and interleukin-6, in MT3 knockout mice induced with CFA. This study highlights the critical role of MT3 in coordinating the intracellular interaction with Zn2+, which is vital for the immune systems’s protective functions. These interactions are fundamental for maintaining metal ion homeostasis and regulating the synthesis of various biomolecules in the body.https://doi.org/10.1038/s41420-025-02322-1
spellingShingle Ngoc Buu Tran
Sook-Jeong Lee
Metallothionein-3-mediated intracellular zinc mediates antioxidant and anti-inflammatory responses in the complete Freund’s adjuvant-induced inflammatory pain mouse model
Cell Death Discovery
title Metallothionein-3-mediated intracellular zinc mediates antioxidant and anti-inflammatory responses in the complete Freund’s adjuvant-induced inflammatory pain mouse model
title_full Metallothionein-3-mediated intracellular zinc mediates antioxidant and anti-inflammatory responses in the complete Freund’s adjuvant-induced inflammatory pain mouse model
title_fullStr Metallothionein-3-mediated intracellular zinc mediates antioxidant and anti-inflammatory responses in the complete Freund’s adjuvant-induced inflammatory pain mouse model
title_full_unstemmed Metallothionein-3-mediated intracellular zinc mediates antioxidant and anti-inflammatory responses in the complete Freund’s adjuvant-induced inflammatory pain mouse model
title_short Metallothionein-3-mediated intracellular zinc mediates antioxidant and anti-inflammatory responses in the complete Freund’s adjuvant-induced inflammatory pain mouse model
title_sort metallothionein 3 mediated intracellular zinc mediates antioxidant and anti inflammatory responses in the complete freund s adjuvant induced inflammatory pain mouse model
url https://doi.org/10.1038/s41420-025-02322-1
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AT sookjeonglee metallothionein3mediatedintracellularzincmediatesantioxidantandantiinflammatoryresponsesinthecompletefreundsadjuvantinducedinflammatorypainmousemodel