IFN‐γ or IL‐4 polarization impacts the response of gingival fibroblasts to oral bacteria

Background and objective We previously reported that gingival fibroblasts (GFs) can be polarized into functionally distinct subtypes, immune‐activating but tissue‐destructive or tissue‐reparative, in response to T helper (Th1) and Th2 stimuli, respectively. The purpose of this study was to evaluate the effect of polarization on GFs responses to oral bacteria. Methods Unprimed (GF(−)) and IFN‐γ (GF(IFN‐γ)) or IL‐4 primed (GF(IL‐4)) GFs were stimulated with live Fusobacterium nucleatum or Porphyromonas gingivalis. The mRNA expression of IL‐1β, IL‐4, LPS‐recognizing components (Toll‐like receptor (TLR) 4, CD14), molecules involved in antigen presentation (human leukocyte antigen (HLA)‐ABC, HLA‐DP, CD74, CD40), chemokines (C‐X‐C motif chemokine (CXCL)10, CXCL11, chemokine (C‐C motif) ligand 20 (CCL20)), collagen type 1 alpha 1 (COL1A1), and matrix metalloproteinase (MMP)‐1, and the protein levels of IL‐1β, CD14, CXCL11, CCL20, and COL1A1 accumulated in supernatants were analyzed using real‐time PCR and ELISA. Results In response to oral bacteria, the GF(IFN‐γ) significantly upregulated the expression of LPS‐recognizing components, molecules involved in antigen presentation, CXCL10, and CXCL11, whereas the levels of IL‐4 and COL1A1 were downregulated, compared with GF(−). The levels of IL‐1β, CCL20, and MMP‐1 from GF(IFN‐γ) were differently regulated between both bacteria; F. nucleatum was synergistically upregulated, but P. gingivalis was downregulated. The GF(IL‐4) stimulated with both bacteria upregulated the levels of IL‐4, whereas the levels of TLR4 and chemokines were downregulated, compared with GF(−). The regulation of IL‐1β, CD14, CXCL11, CCL20, and COL1A1 proteins showed a similar tendency with mRNA regulation. Conclusion Polarization of GFs with IFN‐γ or IL‐4 affected the way that GFs responded to oral bacteria through up or downregulation of inflammatory responses and extracellular matrix control.