PMID- 30644104 OWN - NLM STAT- MEDLINE DCOM- 20191212 LR - 20191217 IS - 1943-3670 (Electronic) IS - 0022-3492 (Linking) VI - 90 IP - 7 DP - 2019 Jul TI - Periodontal ligament-derived mesenchymal stem cells modulate neutrophil responses via paracrine mechanisms. PG - 747-755 LID - 10.1002/JPER.18-0220 [doi] AB - BACKGROUND: Mesenchymal stem cells differentiate into distinct mesenchymal cell lineages and regulate the immune response. The aim of this study was to determine whether periodontal ligament-derived mesenchymal stem cells (PDLSCs) have the ability to modulate neutrophil responses via paracrine mechanisms. METHODS: CD105-enriched PDLSCs were seeded for 24 h and challenged with Porphyromonas gingivalis total protein extract (PgPE) (0 or 2 ug/mL) for 3 h. Cells were then washed and further cultured for 18 h and the supernatants were collected and stored. Next, neutrophil-differentiated human promyelocytic leukemia HL-60 cells (HL60D) were treated with PDLSCs supernatants and HL-60D activation and functional responses were determined. RESULTS: PgPE treatment induced higher secretion of inflammatory markers and chemokines by PDLSCs, including RANTES, eotaxin, interferon (IFN)-gamma- inducible protein 10 (IP-10), monocyte chemoattractant protein-1 (MCP-1), IFN-gamma, interleukin (IL)-6, IL-8 and IL-1ra (P < 0.05). HL-60D recruitment rate was increased by 4.7 +/- 1.09-fold when exposed to PgPE-treated PDLSCs supernatants. PgPE-treated PDLSCs supernatants promoted a 1.78 +/- 1.04-fold increase in the production of intracellular reactive oxygen species (ROS) by PMA-stimulated HL-60D, whereas PgPE-untreated PDLSCs supernatants led to a 16% reduction in intracellular ROS. In sharp contrast, neither PgPE-untreated nor PgPE-treated PDLSCs supernatants altered tumor necrosis factor (TNF)-alpha and IL-1beta secretion by HL-60D cells. CONCLUSION: Together, these findings suggest an important role of PDLSCs in the recognition of P. gingivalis, paracrine recruitment and activation of antimicrobial mechanisms in innate immune cells, without interfering in cytokine responses. CI - (c) 2019 American Academy of Periodontology. FAU - Misawa, Monica Yuri Orita AU - Misawa MYO AD - Division of Periodontics, Department of Stomatology, School of Dentistry, University of Sao Paulo, Sao Paulo, Sao Paulo, Brazil. FAU - Silverio Ruiz, Karina Gonzales AU - Silverio Ruiz KG AD - Division of Periodontics, Department of Prosthodontics and Periodontics, Piracicaba Dental School, University of Campinas, Piracicaba, Sao Paulo, Brazil. FAU - Nociti, Francisco Humberto Jr AU - Nociti FH Jr AD - Division of Periodontics, Department of Prosthodontics and Periodontics, Piracicaba Dental School, University of Campinas, Piracicaba, Sao Paulo, Brazil. FAU - Albiero, Mayra Laino AU - Albiero ML AD - Division of Periodontics, Department of Prosthodontics and Periodontics, Piracicaba Dental School, University of Campinas, Piracicaba, Sao Paulo, Brazil. FAU - Saito, Miki Taketomi AU - Saito MT AD - Division of Periodontics, Department of Prosthodontics and Periodontics, Piracicaba Dental School, University of Campinas, Piracicaba, Sao Paulo, Brazil. FAU - Nobrega Stipp, Rafael AU - Nobrega Stipp R AD - Department of Oral Diagnosis, Piracicaba Dental School, University of Campinas, Piracicaba, Sao Paulo, Brazil. FAU - Condino-Neto, Antonio AU - Condino-Neto A AD - Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Sao Paulo, Brazil. FAU - Holzhausen, Marinella AU - Holzhausen M AD - Division of Periodontics, Department of Stomatology, School of Dentistry, University of Sao Paulo, Sao Paulo, Sao Paulo, Brazil. FAU - Palombo, Henrique AU - Palombo H AD - Division of Periodontics, Department of Stomatology, School of Dentistry, University of Sao Paulo, Sao Paulo, Sao Paulo, Brazil. FAU - Villar, Cristina Cunha AU - Villar CC AD - Division of Periodontics, Department of Stomatology, School of Dentistry, University of Sao Paulo, Sao Paulo, Sao Paulo, Brazil. AD - Department of Periodontics, UTHSC, San Antonio Dental School, San Antonio, TX, USA. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190212 PL - United States TA - J Periodontol JT - Journal of periodontology JID - 8000345 SB - IM MH - Cell Differentiation MH - Cells, Cultured MH - Humans MH - *Mesenchymal Stem Cells MH - Neutrophils MH - Osteogenesis MH - *Periodontal Ligament OTO - NOTNLM OT - cellular biology OT - inflammation OT - innate immune responses OT - neutrophils OT - reactive oxygen species EDAT- 2019/01/16 06:00 MHDA- 2019/12/18 06:00 CRDT- 2019/01/16 06:00 PHST- 2018/04/09 00:00 [received] PHST- 2018/11/03 00:00 [revised] PHST- 2018/11/06 00:00 [accepted] PHST- 2019/01/16 06:00 [pubmed] PHST- 2019/12/18 06:00 [medline] PHST- 2019/01/16 06:00 [entrez] AID - 10.1002/JPER.18-0220 [doi] PST - ppublish SO - J Periodontol. 2019 Jul;90(7):747-755. doi: 10.1002/JPER.18-0220. Epub 2019 Feb 12.