title: DPSCs from Inflamed Pulp Modulate Macrophage Function via the TNF-α/IDO Axis.
abstract: Human dental pulp stem cells (DPSCs) can be isolated from inflamed pulp derived from carious teeth with symptomatic irreversible pulpitis (I-DPSCs), which possess stemness and multidifferentiation potentials similar to DPSCs from healthy pulp. Since macrophages-essential cell players of the pulpal innate immunity-can regulate pulpal inflammation and repair, the authors investigated the immunomodulatory effects of DPSCs/I-DPSCs on macrophage functions and their underlying mechanisms. Similar to DPSCs, I-DPSCs were capable of colony-forming efficiency and adipogenic and osteo/dentinogenic differentiation under in vitro induction conditions. I-DPSCs also expressed a similar phenotypic profile of mesenchymal stem cell markers, except a relatively higher level of CD146 as compared with DPSCs. Coculture of DPSCs or I-DPSCs with differentiated THP-1 cells, the human monocyte cell line, markedly suppressed tumor necrosis factor α (TNF-α) secretion in response to stimulation with lipopolysaccharides (LPS) and/or nigericin. However, unlike TNF-α, the secreted level of interleukin 1β was not affected by coculture with DPSCs or I-DPSCs. Furthermore, DPSC/I-DPSC-mediated inhibition of TNF-α secretion by macrophages was abolished by pretreatment with 1-methyl-D-tryptophan, a specific inhibitor of indoleamine-pyrrole 2,3-dioxygenase (IDO), but not by NSC-398, a specific inhibitor of COX-2, suggesting IDO as a mediator. Interestingly, IDO expression was significantly augmented in macrophages and mesenchymal stromal cells in inflamed human pulp tissues. Collectively, these findings show that I-DPSCs, similar to DPSCs, possess stem cell properties and suppress macrophage functions via the TNF-α/IDO axis, thereby providing a physiologically relevant context for their innate immunomodulatory activity in the dental pulp and their capability for pulp repair.
authors.affiliation: Department of Endodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Oral and Maxillofacial Surgery and Pharmacology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Q Z
authors.initials: QZ
authors.lastname: Zhang
authors.affiliation: Department of Endodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: B
authors.initials: B
authors.lastname: Karabucak
authors.affiliation: Department of Oral and Maxillofacial Surgery and Pharmacology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA anhle@dental.upenn.edu.
authors.forename: A D
authors.initials: AD
authors.lastname: Le
mesh_terms: D000293:Adolescent; D000328:Adult; D015153:Blotting, Western; D002478:Cells, Cultured; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D003782:Dental Pulp / Q000166:cytology* / Q000503:physiopathology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D053583:Interleukin-1beta / Q000378:metabolism; D008264:Macrophages / Q000502:physiology*; D008875:Middle Aged; D011671:Pulpitis / Q000503:physiopathology*; D013234:Stem Cells / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D055815:Young Adult
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha
keywords: cytokines; inflammation; innate immunity; mesenchymal stem cell; microenvironment; pulpitis