Frontiers in immunology
Hemin suppresses interferon responses in periodontal cell models through JAK2-STAT1 inhibition
By Huang X, Gruber R and Panahipour L.
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.