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

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. J. Cell. Physiol. 227: 2441–2450, 2012. © 2011 Wiley Periodicals, Inc.