PMID- 33400271 OWN - NLM STAT- MEDLINE DCOM- 20210518 LR - 20220531 IS - 1600-0765 (Electronic) IS - 0022-3484 (Linking) VI - 56 IP - 3 DP - 2021 Jun TI - IFN-gamma or IL-4 polarization impacts the response of gingival fibroblasts to oral bacteria. PG - 462-470 LID - 10.1111/jre.12837 [doi] AB - 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-gamma (GF(IFN-gamma)) or IL-4 primed (GF(IL-4)) GFs were stimulated with live Fusobacterium nucleatum or Porphyromonas gingivalis. The mRNA expression of IL-1beta, 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-1beta, 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-gamma) 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-1beta, CCL20, and MMP-1 from GF(IFN-gamma) 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-1beta, CD14, CXCL11, CCL20, and COL1A1 proteins showed a similar tendency with mRNA regulation. CONCLUSION: Polarization of GFs with IFN-gamma or IL-4 affected the way that GFs responded to oral bacteria through up or downregulation of inflammatory responses and extracellular matrix control. CI - (c) 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. FAU - Jang, Ju Young AU - Jang JY AD - Department of Periodontology, Institute of Oral Health Science, Ajou University School of Medicine, Suwon, Korea. FAU - Choi, Geum Hee AU - Choi GH AD - Department of Periodontology, Institute of Oral Health Science, Ajou University School of Medicine, Suwon, Korea. FAU - Ji, Suk AU - Ji S AUID- ORCID: 0000-0001-9720-6731 AD - Department of Periodontology, Institute of Oral Health Science, Ajou University School of Medicine, Suwon, Korea. LA - eng GR - National Research Foundation of Korea (NRF)/ GR - NRF-2019R1F1A1058459/Ministry of Education, Science and Technology/ PT - Journal Article DEP - 20210105 PL - United States TA - J Periodontal Res JT - Journal of periodontal research JID - 0055107 RN - 0 (IL4 protein, human) RN - 207137-56-2 (Interleukin-4) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Fibroblasts MH - Fusobacterium nucleatum MH - *Gingiva MH - Humans MH - Interferon-gamma/*analysis MH - Interleukin-4/*analysis MH - Porphyromonas gingivalis OTO - NOTNLM OT - Fusobacterium nucleatum OT - Porphyromonas gingivalis OT - chemokines OT - fibroblast OT - imflammatory mediator OT - innate immunology EDAT- 2021/01/06 06:00 MHDA- 2021/05/19 06:00 CRDT- 2021/01/05 12:18 PHST- 2020/12/08 00:00 [revised] PHST- 2020/03/30 00:00 [received] PHST- 2020/12/15 00:00 [accepted] PHST- 2021/01/06 06:00 [pubmed] PHST- 2021/05/19 06:00 [medline] PHST- 2021/01/05 12:18 [entrez] AID - 10.1111/jre.12837 [doi] PST - ppublish SO - J Periodontal Res. 2021 Jun;56(3):462-470. doi: 10.1111/jre.12837. Epub 2021 Jan 5.