title: Sequential IL-23 and IL-17 and increased Mmp8 and Mmp14 expression characterize the progression of an experimental model of periodontal disease in type 1 diabetes.
abstract: Molecular mechanisms responsible for periodontal disease (PD) and its worsening in type 1 Diabetes Mellitus (DM1) remain unknown. Cytokine profile and expression levels of collagenases, Mmp14, and tissue inhibitors were determined, as were the numbers of neutrophils and macrophages in combined streptozotocin-induced DM1 and ligature-induced PD models. Increased IL-23 (80-fold) and Mmp8 expression (25-fold) was found in DM1. Ligature resulted in an IL-1β/IL-6 profile, increased expression of Mmp8, Mmp13, and Mmp14 (but not Mmp1), and transient expression of Timp1 and Reck in non-diabetics. PD in DM1 involved IL-1β (but not IL-6) and IL-23/IL-17, reduced IL-6 and IL-10, sustained Mmp8 and Mmp14, increased Mmp13 and reduced Reck expression in association with 20-fold higher counts of neutrophils and macrophages. IL-23 and Mmp8 expression are hallmarks of DM1. In association with the IL-1/IL-6 (Th1) response in PD, one found a secondary IL-17 (Th17) pathway in non-diabetic rats. Low IL-6/TNF-α suggest that the Th1 response was compromised in DM1, while IL-17 indicates a prevalence of the Th17 pathway, resulting in high neutrophil recruitment. Mmp8, Mmp13, and Mmp14 expression seems important in the tissue destruction during PD in DM1. PD-associated IL-1/IL-6 (Th1), IL-10, and Reck expression are associated with the acute-to-chronic inflammation transition, which is lost in DM1. In conclusion, IL-23/IL-17 are associated with the PD progression in DM1.
authors.affiliation: Department of Anatomy, Cell Biology, Physiology and Biophysics, State University of Campinas - UNICAMP, Campinas, São Paulo, Brazil.
authors.forename: Juliete A F
authors.initials: JA
authors.lastname: Silva
authors.forename: Danilo L
authors.initials: DL
authors.lastname: Ferrucci
authors.forename: Luis A
authors.initials: LA
authors.lastname: Peroni
authors.forename: Patrícia G S
authors.initials: PG
authors.lastname: Abrahão
authors.forename: Aline F
authors.initials: AF
authors.lastname: Salamene
authors.forename: Carlos
authors.initials: C
authors.lastname: Rossa-Junior
authors.forename: Hernandes F
authors.initials: HF
authors.lastname: Carvalho
authors.forename: Dagmar R
authors.initials: DR
authors.lastname: Stach-Machado
mesh_terms: D016301:Alveolar Bone Loss / Q000201:enzymology / Q000209:etiology / Q000276:immunology; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D018450:Disease Progression; D058851:GPI-Linked Proteins / Q000378:metabolism; D005881:Gingiva / Q000201:enzymology* / Q000276:immunology*; D018836:Inflammation Mediators / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D053759:Interleukin-23 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D008026:Ligation; D008264:Macrophages / Q000276:immunology; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D053511:Matrix Metalloproteinase 14 / Q000235:genetics / Q000378:metabolism*; D020784:Matrix Metalloproteinase 8 / Q000235:genetics / Q000378:metabolism*; D008963:Molar / Q000601:surgery; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000276:immunology; D010510:Periodontal Diseases / Q000150:complications* / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D058504:Th17 Cells / Q000276:immunology; D013997:Time Factors; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D058851:GPI-Linked Proteins; C515934:Il17a protein, rat; D018836:Inflammation Mediators; D020381:Interleukin-17; D053583:Interleukin-1beta; D053759:Interleukin-23; D015850:Interleukin-6; D012333:RNA, Messenger; C529735:Reck protein, rat; D025521:Tumor Suppressor Proteins; D016753:Interleukin-10; D053509:Matrix Metalloproteinase 13; C507083:Mmp13 protein, rat; D020784:Matrix Metalloproteinase 8; D053511:Matrix Metalloproteinase 14