title: Immune Cells and Molecular Networks in Experimentally Induced Pulpitis.
abstract: Dental pulp is a dynamic tissue able to resist external irritation during tooth decay by using immunocompetent cells involved in innate and adaptive responses. To better understand the immune response of pulp toward gram-negative bacteria, we analyzed biological mediators and immunocompetent cells in rat incisor pulp experimentally inflamed by either lipopolysaccharide (LPS) or saline solution (phosphate-buffered saline [PBS]). Untreated teeth were used as control. Expression of pro- and anti-inflammatory cytokines, chemokine ligands, growth factors, and enzymes were evaluated at the transcript level, and the recruitment of the different leukocytes in pulp was measured by fluorescence-activated cell-sorting analysis after 3 h, 9 h, and 3 d post-PBS or post-LPS treatment. After 3 d, injured rat incisors showed pulp wound healing and production of reparative dentin in both LPS and PBS conditions, testifying to the reversible pulpitis status of this model. IL6, IL1-β, TNF-α, CCL2, CXCL1, CXCL2, MMP9, and iNOS gene expression were significantly upregulated after 3 h of LPS stimulation as compared with PBS. The immunoregulatory cytokine IL10 was also upregulated after 3 h, suggesting that LPS stimulates not only inflammation but also immunoregulation. Fluorescence-activated cell-sorting analysis revealed a significant, rapid, and transient increase in leukocyte levels 9 h after PBS and LPS stimulation. The quantity of dendritic cells was significantly upregulated with LPS versus PBS. Interestingly, we identified a myeloid-derived suppressor cell-enriched cell population in noninjured rodent incisor dental pulp. The percentage of this population, known to regulate immune response, was higher 9 h after inflammation triggered with PBS and LPS as compared with the control. Taken together, these data offer a better understanding of the mechanisms involved in the regulation of dental pulp immunity that may be elicited by gram-negative bacteria.
authors.affiliation: INSERM, Center for Research in Transplantation and Immunology, UMR 1064, Nantes, France.
authors.forename: E
authors.initials: E
authors.lastname: Renard
authors.affiliation: INSERM, Center for Research in Transplantation and Immunology, UMR 1064, Nantes, France Faculty of Odontology, University of Nantes, Nantes, France.
authors.forename: A
authors.initials: A
authors.lastname: Gaudin
authors.affiliation: INSERM, Center for Research in Transplantation and Immunology, UMR 1064, Nantes, France Faculty of Odontology, University of Nantes, Nantes, France.
authors.forename: G
authors.initials: G
authors.lastname: Bienvenu
authors.affiliation: INSERM, UMR 957, Nantes, France.
authors.forename: J
authors.initials: J
authors.lastname: Amiaud
authors.affiliation: Laboratory of Tissue Biology and Therapeutic Engineering, UMR 5305, and Faculty of Odontology, Lyon, France.
authors.forename: J C
authors.initials: JC
authors.lastname: Farges
authors.affiliation: INSERM, Center for Research in Transplantation and Immunology, UMR 1064, Nantes, France.
authors.forename: M C
authors.initials: MC
authors.lastname: Cuturi
authors.affiliation: INSERM, Center for Research in Transplantation and Immunology, UMR 1064, Nantes, France.
authors.forename: A
authors.initials: A
authors.lastname: Moreau
authors.affiliation: INSERM, Center for Research in Transplantation and Immunology, UMR 1064, Nantes, France Faculty of Odontology, University of Nantes, Nantes, France Brigitte.alliot-licht@univ-nantes.fr.
authors.forename: B
authors.initials: B
authors.lastname: Alliot-Licht
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000032:analysis; D054360:Chemokine CXCL1 / Q000032:analysis; D018925:Chemokines / Q000032:analysis; D016207:Cytokines / Q000032:analysis; D003713:Dendritic Cells / Q000473:pathology; D003782:Dental Pulp / Q000201:enzymology / Q000276:immunology*; D003809:Dentin, Secondary / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D006090:Gram-Negative Bacteria / Q000276:immunology; D018836:Inflammation Mediators / Q000032:analysis; D016753:Interleukin-10 / Q000032:analysis; D053583:Interleukin-1beta / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D007962:Leukocytes / Q000145:classification; D008070:Lipopolysaccharides / Q000276:immunology; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D052247:Nitric Oxide Synthase Type II / Q000032:analysis; D011671:Pulpitis / Q000201:enzymology / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000473:pathology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D054360:Chemokine CXCL1; D018925:Chemokines; C513297:Cxcl1 protein, rat; D016207:Cytokines; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat
keywords: chemokines; cytokines; dental pulp; innate immune response; leukocytes; lipopolysaccharides