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Research Article: Transcriptomic profiling reveals selective attenuation of interferon-associated inflammatory signaling and induction of metallothioneins by a zinc-containing oral rinse

Date Published: 2026-07-27

Abstract:
Oral stromal and epithelial cells contribute to mucosal inflammation through cytokine-induced chemokine production. Essential oil-containing mouth rinses are widely used as adjuncts to oral hygiene, but whether zinc-containing formulations directly modulate host inflammatory signaling remains unclear. This study investigated the effects of a zinc-containing Listerine ® formulation on IL-1?/TNF-?-induced inflammatory responses in human oral cells. Primary human gingival fibroblasts were stimulated with IL-1?/TNF-? in the presence or absence of Listerine ® . Transcriptional responses were analyzed by RNA sequencing and validated by quantitative PCR and immunoassays. HSC2 epithelial cells were used to assess selected responses across oral cell types. Phospho-STAT1 immunostaining evaluated canonical STAT1 activation, and ICP–MS determined trace-element composition. IL-1?/TNF-? induced a broad inflammatory transcriptional program characterized by chemokines, NF-?B-associated mediators, and interferon-associated genes. Listerine ® attenuated this response, with strongest effects on CXCL10, CXCL11, IFIT family members, GBP family members, and OASL , whereas classical NF-?B-associated chemokines such as CXCL1, CXCL2 , and CXCL8 were less affected. Listerine ® also induced a zinc-responsive stress-adaptation signature dominated by metallothioneins. ICP–MS analysis confirmed the presence of zinc in Listerine ® , and zinc alone partially reproduced the suppression of CXCL10 . In contrast, individual essential oil constituents failed to recapitulate the anti-inflammatory effects of the complete formulation. Notably, Listerine ® did not prevent IFN-?-induced STAT1 phosphorylation, indicating that suppression of interferon-associated genes was not due to general blockade of canonical STAT1 activation. These findings identify a previously unrecognized host-modulatory activity of a zinc-containing Listerine ® formulation characterized by selective attenuation of interferon-associated inflammatory transcription together with induction of a zinc-responsive metallothionein program.

Introduction:
Oral stromal and epithelial cells contribute to mucosal inflammation through cytokine-induced chemokine production. Essential oil-containing mouth rinses are widely used as adjuncts to oral hygiene, but whether zinc-containing formulations directly modulate host inflammatory signaling remains unclear. This study investigated the effects of a zinc-containing Listerine ® formulation on IL-1?/TNF-?-induced inflammatory responses in human oral cells.

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