Transcriptomic profiling reveals selective attenuation of interferon-associated inflammatory signaling and induction of metallothioneins by a zinc-containing oral rinse
TL;DR
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.
Abstract
Background 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-1β/TNF-α-induced inflammatory responses in human oral cells. Methods Primary human gingival fibroblasts were stimulated with IL-1β/TNF-α 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. Results IL-1β/TNF-α induced a broad inflammatory transcriptional program characterized by chemokines, NF-κB-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-κB-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-γ-induced STAT1 phosphorylation, indicating that suppression of interferon-associated genes was not due to general blockade of canonical STAT1 activation. Conclusion 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.