Title: 1436 - Identification of Pro-Inflammatory and Specialized Pro-resolving Mediators in Human Gingiva
Chun-Teh Lee (Presenter)
The University of Texas Health Science Center at Houston School of Dentistry
Anthony Osborne, The University of Texas Health Science Center at Houston School of Dentistry
Emily Wu, The University of Texas Health Science Center at Houston School of Dentistry
Nikola Angelov, UTHealth School of Dentistry
Charles Serhan, Brigham and Women's Hospital
Thomas Van Dyke, The Forsyth Institute
Objectives: Specialized pro-resolving mediators (SPMs) are lipid mediators derived from essential fatty acids that have dual anti-inflammatory and pro-resolution actions. SPMs have been proven effective in treating experimental periodontitis in pre-clinical models. Profiles of SPMs differ in inflammatory diseases, such as mastitis and atherosclerosis, in humans. This study identifies profiles of SPMs and related molecules in gingiva of subjects with chronic periodontitis compared to those of periodontally healthy subjects.
Methods: Gingival tissues were collected from diseased sites (probing depth ≥5 mm; clinical attachment loss ≥3 mm) in subjects with periodontitis (P) and healthy sites (probing depth ≤3 mm; clinical attachment loss≤2 mm; no radiographic bone loss) in healthy subjects (C). Lipid mediator metabololipidomics was performed to identify molecules of interest. Samples were analyzed using a high performance liquid chromatography system (HPLC; Shimadzu) coupled with a QTrap5500 mass spectrometer (AB Sciex) in negative ionization mode with scheduled multiple reaction monitoring (sMRM). Lipid mediators were quantified using the ratio of reference standards and deuterium-labelled standards. Student’s t-test was used to compare results in two groups.
Results: Average probing depth was 3.0±0.0 mm and 6.5±3.1 mm in C (n=3) and P (n=3), respectively. Here > 20 bioactive lipid mediators and pathway markers in gingiva were identified. These included inflammation initiating mediators (leukotriene B4 (LTB4) and prostaglandin E2), pro-resolving mediators (Lipoxin B4 (LXB4)), and precursors for lipoxins (15-HETE), resolvins (17HDHA, 18-HEPE), protectins (pathway marker 17-HDHA), and maresins (14-HDHA). Levels of precursors of SPMs in P were generally higher than C. The ratios of LXB4/LTB4 (H: 2.28±1.47; P: 0.71±0.06, p=0.14) and LXB4/15-HETE (H: 3.78±3.55; P: 1.33±1.28, p=0.32) indicate a pro-resolving profile in health.
Conclusions: Lipoxin and precursors of SPMs were identified in human gingiva. The decreased ratios of LXB4/LTB4 and LXB4/15-HETE in patients with chronic periodontitis suggest a failure of natural resolution of inflammation.
This abstract is based on research that was funded entirely or partially by an outside source:
Grants Program in Dental Research, The Houston Section of The AADR, UTHealth School of Dentistry; CCTS Translational Technologies Core Laboratories Awards, UTHealth
The submitter must disclose the names of the organizations with which any author have a relationship, the nature of the relationship, and the clinical or research area involved. The following is submitted: NONE