Zinc sulfate modulates the C3H10T1/2 mesenchymal stem cell line secretome and NFκB signaling during inflammation to influence selected immune cell responses.

Authors

Edson Naoto Makiyama, Iolanda Silva Rafael Pizzolato-Cezar, Sumara de Freitas, Ricardo Ambrósio Fock

Published in

Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine. Aug 04, 2026. Epub Aug 04, 2026.

Abstract

Zinc (Zn) is essential for immune cell function, while mesenchymal stem cells (MSCs) exert immunomodulatory effects primarily through the secretion of soluble factors. Considering the ability of MSCs and Zn to modulate the immune and inflammatory systems, this study investigated, in vitro, the effects of Zn supplementation on MSC responses to inflammatory stimuli and the subsequent modulation of macrophages and lymphocytes. Using the C3H10T1/2 line as a MSC model, we determined that 1 µM ZnSO₄ enhanced MSC metabolic activity without affecting viability or cell-cycle distribution, whereas higher concentrations reduced cell viability. Under lipopolysaccharide (LPS) stimulation, Zn inhibited NFκB phosphorylation and increased AMPK phosphorylation, indicating anti-inflammatory and adaptive metabolic responses. Similarly, under TNF-α stimulation, Zn also reduced NFκB phosphorylation. Zn supplementation altered MSC secretory profiles, reducing IL-6, IL-10, and nitric oxide (NO) production while increasing TGF-β and prostaglandin E2 (PGE₂) levels, indicating that Zn modifies MSC-derived soluble factor production under inflammatory conditions. Conditioned media from Zn-treated MSCs attenuated IL-6 and IL-12 production in macrophages, indicating a reduced pro-inflammatory cytokine response, whereas lymphocyte responses were unaffected. Importantly, Zn modulation of cytokine production was observed under LPS stimulation but not under TNF-α exposure, suggesting that Zn preferentially interferes with signaling pathways triggered by microbial stimuli. Overall, this study provides mechanistic insight into how Zn affects the secretory profile and inflammatory signaling pathways of C3H10T1/2 cells. These findings support further studies in primary MSCs to determine whether Zn supplementation may represent a useful strategy for modulating MSC-mediated immune regulation in therapeutic settings.

PMID:
42550401
Bibliographic data and abstract were imported from PubMed on 04 Aug 2026.

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