Hemin suppresses interferon responses in periodontal cell models through JAK2–STAT1 inhibition
- 1Department of Oral Biology, Medical University of Vienna , ,
Abstract
Introduction: Hemin, an oxidized heme species released during erythrocyte breakdown, is detectable in gingival crevicular fluid during periodontal inflammation, but its effects on local immune signaling remain unclear. We investigated whether hemin modifies cytokine-induced interferon responses in HSC-2 oral squamous cell carcinoma cells and primary human gingival fibroblasts.
Methods: Cells were stimulated with interleukin-1β and tumor necrosis factor-α, or with interferon-γ, in the presence or absence of hemin. Transcriptomic changes were assessed by RNA sequencing and pathway analysis, and selected transcripts and proteins were validated by reverse-transcription quantitative PCR, enzyme-linked immunosorbent assay, immunoblotting, and immunofluorescence. Ligand–kinase interactions were examined by molecular docking and molecular dynamics simulations, and recombinant Janus kinase 2 activity was measured in a cell-free assay.
Results: Hemin preferentially suppressed an interferon-associated gene network, including CXCL10, CXCL11, MX1, OAS1, IFIT1, IFIT3, and ISG15, while nuclear factor κB-associated responses were comparatively preserved. Hemin also reduced signal transducer and activator of transcription 1 Tyr701 phosphorylation and nuclear accumulation induced by either the cytokine combination or interferon-γ. Computational analyses predicted stable hemin interactions within conserved ATP-binding pockets of Janus kinases, and the cell-free assay demonstrated inhibition of recombinant Janus kinase 2.
Discussion: Together, these findings show that hemin attenuates interferon-associated transcription in periodontal cell models, consistent with inhibition of the Janus kinase 2–signal transducer and activator of transcription 1 axis. This mechanism may enable blood-derived hemin to modify local mucosal immune signaling, although its relevance to periodontal tissues and antiviral defense requires confirmation in organotypic, infection, and in vivo models.
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BibTeX
@article{huang2026hemin,
title = {{Hemin suppresses interferon responses in periodontal cell models through JAK2–STAT1 inhibition}},
author = {Xiaoyu Huang and Reinhard Gruber and Layla Panahipour},
journal = {Frontiers in immunology},
year = {2026},
month = sep,
doi = {10.3389/fimmu.2026.1958476},
url = {https://europepmc.org/article/PMC/PMC13661988},
note = {CC BY},
}
RIS
TY - JOUR
TI - Hemin suppresses interferon responses in periodontal cell models through JAK2–STAT1 inhibition
AU - Xiaoyu Huang
AU - Reinhard Gruber
AU - Layla Panahipour
PY - 2026
DA - 2026/09/30
JO - Frontiers in immunology
DO - 10.3389/fimmu.2026.1958476
UR - https://europepmc.org/article/PMC/PMC13661988
AB - Introduction: Hemin, an oxidized heme species released during erythrocyte breakdown, is detectable in gingival crevicular fluid during periodontal inflammation, but its effects on local immune signaling remain unclear. We investigated whether hemin modifies cytokine-induced interferon responses in HSC-2 oral squamous cell carcinoma cells and primary human gingival fibroblasts. Methods: Cells were stimulated with interleukin-1β and tumor necrosis factor-α, or with interferon-γ, in the presence or absence of hemin. Transcriptomic changes were assessed by RNA sequencing and pathway analysis, and selected transcripts and proteins were validated by reverse-transcription quantitative PCR, enzyme-linked immunosorbent assay, immunoblotting, and immunofluorescence. Ligand–kinase interactions were examined by molecular docking and molecular dynamics simulations, and recombinant Janus kinase 2 activity was measured in a cell-free assay. Results: Hemin preferentially suppressed an interferon-associated gene network, including CXCL10, CXCL11, MX1, OAS1, IFIT1, IFIT3, and ISG15, while nuclear factor κB-associated responses were comparatively preserved. Hemin also reduced signal transducer and activator of transcription 1 Tyr701 phosphorylation and nuclear accumulation induced by either the cytokine combination or interferon-γ. Computational analyses predicted stable hemin interactions within conserved ATP-binding pockets of Janus kinases, and the cell-free assay demonstrated inhibition of recombinant Janus kinase 2. Discussion: Together, these findings show that hemin attenuates interferon-associated transcription in periodontal cell models, consistent with inhibition of the Janus kinase 2–signal transducer and activator of transcription 1 axis. This mechanism may enable blood-derived hemin to modify local mucosal immune signaling, although its relevance to periodontal tissues and antiviral defense requires confirmation in organotypic, infection, and in vivo models.
SN - 1664-3224
ER -