Ruxolitinib Suppresses Interferon-γ-Induced JAK/STAT Activation in Oral Keratinocytes.

OBJECTIVES The Janus kinase (JAK)/Signal Transducer and Activator of Transcription (STAT) pathway plays a crucial role in oral inflammatory diseases such as oral lichen planus (OLP) and periodontitis. Interferon-gamma (IFN-γ) is a cytokine that activates the JAK/STAT pathway. This study aimed to evaluate the effect of the JAK1/2 inhibitor ruxolitinib on IFN-γ-driven inflammation in oral keratinocytes. MATERIAL AND METHODS Human oral keratinocytes (OKG4) were stimulated with 10 ng/mL IFN-γ to assess the expression and phosphorylation status of JAK1, JAK2, STAT1, STAT2, and human leukocyte antigen (HLA)-DRB1. Ruxolitinib (1 µM) was used to inhibit IFN-γ-induced signaling. Analyses were performed using Western blotting, immunofluorescence microscopy, and cell viability assays. RESULTS IFN-γ significantly upregulated pSTAT1 at 30 min (control: 1.00 ± 0.00, IFN-γ: 29.17 ± 9.26, p = 0.0013), with sustained activation after 24 h (IFN-γ: 29.49 ± 18.26, p = 0.0127). HLA-DRB1 expression was also increased (control: 1.00 ± 0.00, IFN-γ: 3.51 ± 1.28, p = 0.0127). Co-treatment with IFN-γ and ruxolitinib reduced both pSTAT1 (p = 0.3448) and HLA-DRB1 (p = 0.3448) expression to baseline levels. Ruxolitinib had no effect on cell viability (p > 0.9999). CONCLUSIONS IFN-γ induces robust and sustained activation of STAT1 and upregulation of HLA-DRB1 in oral keratinocytes, both effectively suppressed by ruxolitinib. These findings underscore the therapeutic potential of targeting the JAK/STAT pathway in oral inflammatory diseases.

• Publication year

  2026

• Venue

  Clinical and Experimental Dental Research

• Publication date

  2026-01-09

• Fields of study

  Medicine

• Identifiers
  DOI 10.1002/cre2.70281PMID 41517938
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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