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Treatment of periodontitis by homing M2 macrophages

归巢M2巨噬细胞治疗牙周炎

基本信息

批准号：
9296130
负责人：
CHARLES SFEIR
金额：
$ 23.05万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-07-01 至 2020-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9296130
关键词：
Address Adult Affect Alveolar Bone Loss Anti-Inflammatory Agents Anti-inflammatory Bacteria Bacterial Infections Behavior Biological Biological Assay Birth CCL17 gene CCL2 gene CCL22 gene Calculi Canis familiaris Cardiovascular Diseases Cells Chemotaxis Chronic Clinical Treatment Control Groups Data Debridement Dental Calculus Dental Plaque Dental caries Diabetes Mellitus Disease Disease model Enzyme-Linked Immunosorbent Assay Gingival Pocket Glycolates Homing Immune Immune response Immunohistochemistry Impaired wound healing In Vitro Inbred BALB C Mice Infiltration Inflammation Inflammatory Inflammatory Response Injectable Interleukin-10 Interleukin-13 Interleukin-4 Intestines Laboratories Lymphocyte Methods Microbe Modeling Morphology Mouth Diseases Mus Outcome Study Periodontal Diseases Periodontal Pocket Periodontitis Phenotype Play Population Property Public Health Recombinants Recruitment Activity Regulatory T-Lymphocyte Research Resolution Role Root Scaling Signal Recognition Particle Site Systemic disease Techniques Technology Testing Therapeutic Tissues Tooth Loss Topical Antibiotic Transforming Growth Factor beta Translating United States X-Ray Computed Tomography aged alveolar bone bone loss chemokine cytokine immunoregulation in vivo macrophage monocyte mouse model new therapeutic target pathogen response standard care tooth surface treatment strategy

项目摘要

PROJECT SUMMARY Periodontitis is the second most common oral disease, affecting about half of adults (65 millions) in the United States. Periodontitis causes tooth loss and has been implicated in several serious systemic diseases include diabetes, cardiovascular diseases, and immature birth. Periodontitis is a chronic inflammatory disease, triggered by bacterial infection present in dental plaques and calculus, but the disease itself is caused by host immune response to these pathogens. Current standard treatment is debridement of plaques and calculus to reduce the bacterial load, however, there are no therapies to address the immune aspect of the diseases. Thus, many research groups have started developing technologies to regulate the immune response and reduce inflammation. Our group has focused so far on recruiting T regulatory immune cells new target for therapy of periodontitis. In the previous study, we have successfully reduced alveolar bone loss by recruiting regulatory T cells in mouse and dog periodontitis model. Regulatory T cells were recruited by injecting C-C motif chemokine 22 (CCL22) releasing PLGA microparticles in the periodontal pockets. These results indicated that recruiting regulatory immune cells by local delivery of chemokine indeed reduces inflammation and bone loss in periodontitis. To further explore the principle of “recruitment of regulatory immune cells” and to continue our efforts to develop better therapies, we hypothesize that recruiting a larger population of anti-inflammatory immune cells such as M2 macrophages will achieve a better therapeutic option. Macrophages plays an important role in inflammatory responses, and interestingly have a polarization property by differentiating into M1 (pro- inflammatory) or M2 (anti-inflammatory) macrophages. Our hypothesis that is strongly supported by our recent in vivo pilot data is that the local delivery of CCL2 will induce homing of M2 macrophages, and differentiation of macrophages and monocytes to an M2 phenotype leading to decreased inflammation and bone loss in periodontal tissue. To test this hypothesis, we set the following specific aims; 1) To fabricate CCL2 releasing microparticles and analyze recruitment of M2 macrophage and differentiation of macrophages and monocytes to M2 macrophages and 2) To analyze effect of CCL2 on periodontitis in mouse model. We anticipate that CCL2 released from PLGA microparticles will recruit and induce M2 macrophages, and reduce inflammation and bone loss of periodontal tissue in mouse periodontitis model. Moreover, this concept could be applied to therapies for other inflammatory diseases such as delayed wound healing of diabetes or bowel disease.

项目总结