PMID- 30225677 OWN - NLM STAT- MEDLINE DCOM- 20191220 LR - 20200225 IS - 1436-3771 (Electronic) IS - 1432-6981 (Linking) VI - 23 IP - 4 DP - 2019 Apr TI - Immunostimulatory activity of low-molecular-weight hyaluronan on dendritic cells stimulated with Aggregatibacter actinomycetemcomitans or Porphyromonas gingivalis. PG - 1887-1894 LID - 10.1007/s00784-018-2641-5 [doi] AB - OBJECTIVES: Periodontitis is a chronic inflammatory disease characterized by tooth-supporting tissue destruction, which is elicited by the host's immune response triggered against periodonto-pathogen bacteria. During periodontal tissue destruction, extracellular matrix components are metabolized and fragmented. Some extracellular matrix component-derived fragments, such as low-molecular-weight hyaluronan (LMW-HA), have potent immunogenic potential, playing a role as damage-associated molecular patterns (DAMPs) during activation of immune cells. Dendritic cells (DCs) play a central role in the host's immune response displayed during periodontitis; thus, this study aimed to analyze whether LMW-HA has an immunostimulatory activity on DCs when stimulated with periodonto-pathogen bacteria. MATERIALS AND METHODS: LMW-HA-treated and non-treated DCs were stimulated with Aggregatibacter actinomycetemcomitans or Porphyromonas gingivalis and the mRNA expression for cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1B), interleukin-6 (IL-6), and interleukin-23 (IL-23A) was quantified by RT-qPCR. In addition, transcription factors interferon regulatory factor 4 (IRF4), interferon regulatory factor 8 (IRF8), neurogenic locus notch homolog protein 2 (NOTCH2), and basic leucine zipper ATF-like transcription factor 3 (BATF3), involved in DC activation, were analyzed. RESULTS: Higher expression levels of TNF-alpha, IL-1B, IL-6, and IL-23A were detected in LMW-HA-treated DCs after bacterial infection, as compared with non-treated DCs. When LMW-HA-treated DCs were infected with A. actinomycetemcomitans, higher levels of IRF4, NOTCH2, and BATF3 were detected compared with non-treated cells; whereas against P. gingivalis infection, increased levels of IRF4 and NOTCH2 were detected. CONCLUSION: LMW-HA plays an immunostimulatory role on the immune response triggered by DCs during infection with A. actinomycetemcomitans or P. gingivalis. CLINICAL RELEVANCE: Detection of extracellular matrix component-derived fragments produced during periodontal tissue destruction, such as LMW-HA, could explain at least partly unsuccessful periodontal treatment and the chronicity of the disease. FAU - Monasterio, Gustavo AU - Monasterio G AD - Periodontal Biology Laboratory, Faculty of Dentistry, Universidad de Chile, Sergio Livingstone Pohlhammer 943, 8380492, Independencia, Santiago, Chile. FAU - Guevara, Jose AU - Guevara J AD - Periodontal Biology Laboratory, Faculty of Dentistry, Universidad de Chile, Sergio Livingstone Pohlhammer 943, 8380492, Independencia, Santiago, Chile. FAU - Ibarra, Juan Pablo AU - Ibarra JP AD - Periodontal Biology Laboratory, Faculty of Dentistry, Universidad de Chile, Sergio Livingstone Pohlhammer 943, 8380492, Independencia, Santiago, Chile. FAU - Castillo, Francisca AU - Castillo F AD - Periodontal Biology Laboratory, Faculty of Dentistry, Universidad de Chile, Sergio Livingstone Pohlhammer 943, 8380492, Independencia, Santiago, Chile. FAU - Diaz-Zuniga, Jaime AU - Diaz-Zuniga J AD - Periodontal Biology Laboratory, Faculty of Dentistry, Universidad de Chile, Sergio Livingstone Pohlhammer 943, 8380492, Independencia, Santiago, Chile. FAU - Alvarez, Carla AU - Alvarez C AD - Periodontal Biology Laboratory, Faculty of Dentistry, Universidad de Chile, Sergio Livingstone Pohlhammer 943, 8380492, Independencia, Santiago, Chile. FAU - Cafferata, Emilio A AU - Cafferata EA AD - Periodontal Biology Laboratory, Faculty of Dentistry, Universidad de Chile, Sergio Livingstone Pohlhammer 943, 8380492, Independencia, Santiago, Chile. AD - Faculty of Dentistry, Universidad Peruana Cayetano Heredia, Lima, Peru. FAU - Vernal, Rolando AU - Vernal R AUID- ORCID: 0000-0002-1391-320X AD - Periodontal Biology Laboratory, Faculty of Dentistry, Universidad de Chile, Sergio Livingstone Pohlhammer 943, 8380492, Independencia, Santiago, Chile. rvernal@uchile.cl. AD - Dentistry Unit, Faculty of Health Sciences, Universidad Autonoma de Chile, Santiago, Chile. rvernal@uchile.cl. LA - eng GR - FONDECYT 1181780/Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT)/ GR - FONDECYT 1140904/Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT)/ PT - Journal Article DEP - 20180917 PL - Germany TA - Clin Oral Investig JT - Clinical oral investigations JID - 9707115 RN - 0 (Adjuvants, Immunologic) RN - 0 (Cytokines) RN - 9004-61-9 (Hyaluronic Acid) MH - Adjuvants, Immunologic/*pharmacology MH - *Aggregatibacter actinomycetemcomitans MH - Cells, Cultured MH - Cytokines/immunology MH - Dendritic Cells/*drug effects/microbiology MH - Extracellular Matrix MH - Humans MH - Hyaluronic Acid/*pharmacology MH - Molecular Weight MH - Periodontitis MH - *Porphyromonas gingivalis OTO - NOTNLM OT - Aggregatibacter actinomycetemcomitans OT - Cytokines OT - Dendritic cells OT - Hyaluronan OT - LMW-HA OT - Porphyromonas gingivalis OT - Transcription factors EDAT- 2018/09/19 06:00 MHDA- 2019/12/21 06:00 CRDT- 2018/09/19 06:00 PHST- 2018/05/07 00:00 [received] PHST- 2018/09/11 00:00 [accepted] PHST- 2018/09/19 06:00 [pubmed] PHST- 2019/12/21 06:00 [medline] PHST- 2018/09/19 06:00 [entrez] AID - 10.1007/s00784-018-2641-5 [pii] AID - 10.1007/s00784-018-2641-5 [doi] PST - ppublish SO - Clin Oral Investig. 2019 Apr;23(4):1887-1894. doi: 10.1007/s00784-018-2641-5. Epub 2018 Sep 17.