Departmental Papers (Dental)

Document Type

Journal Article

Date of this Version

10-1-2016

Publication Source

Journal of Dental Research

Volume

95

Issue

11

Start Page

1274

Last Page

1281

DOI

10.1177/0022034516657817

Copyright/Permission Statement

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. © International & American Associations for Dental Research 2016.

Keywords

cytokines, inflammation, innate immunity, mesenchymal stem cell, microenvironment, pulpitis, Adolescent, Adult, Blotting, Western, Cells, Cultured, Cyclooxygenase 2 Inhibitors, Dental Pulp, Enzyme-Linked Immunosorbent Assay, Humans, Indoleamine-Pyrrole 2, 3, -Dioxygenase, Interleukin-1beta, Macrophages, Middle Aged, Pulpitis, Stem Cells, Tumor Necrosis Factor-alpha, Young Adult, cyclooxygenase 2 inhibitor, indoleamine 2, 3 dioxygenase, interleukin 1beta, tumor necrosis factor, adolescent, adult, antagonists and inhibitors, cell culture, cytology, enzyme linked immunosorbent assay, human, macrophage, metabolism, middle aged, pathophysiology, physiology, pulpitis, stem cell, tooth pulp, Western blotting, young adult

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Date Posted: 10 February 2023

This document has been peer reviewed.