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Intestinal Inflammation: Signaling proteins and the rate of PMN transmigration

肠道炎症：信号蛋白和 PMN 迁移率

基本信息

批准号：
10428645
负责人：
CHARLES A PARKOS
金额：
$ 57.1万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-10-01 至 2026-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10428645
关键词：
Affinity Agonist Binding Biopsy Bone Marrow CD47 gene Cell Communication Cells Chimera organism Colitis Colon Complex Data Disease Epithelial Epithelial Cells Event Focal Adhesions G Protein-Coupled Receptor Signaling G-Protein-Coupled Receptors GTP-Binding Protein alpha Subunits, Gs Goals Health Hematopoietic Human Immune Impaired healing In Vitro Individual Inflammation Inflammatory Inflammatory Bowel Diseases Inflammatory Response Injury Integrins Interferon Type II Interleukin-1 beta Interleukin-17 Intestinal Mucosa Intestines Kinetics Knockout Mice LTB4R gene Leukocytes Leukotriene B4 Ligands Ligation Light Mediating Membrane Proteins Modeling Mucositis Mucous Membrane Mus Nature Production Regulation Reporting Role Signal Transduction Signaling Protein Site TNF gene TNFRSF1A gene Thrombospondin 1 Thrombospondins Tissues antagonist cell motility cell type dextran sulfate sodium induced colitis druggable target first responder gut inflammation healing in vivo injured injury and repair injury recovery intestinal epithelium knock-down lipid mediator migration neutrophil novel receptor recruit repaired response wound wound healing

项目摘要

Abstract Recent reports by our group and others have highlighted the beneficial and detrimental nature of innate immune cell interactions with intestinal epithelia. Indeed, as observed in Inflammatory Bowel Disease (IBD), an excessive inflammatory response not only results in mucosal injury but is also detrimental for wound repair. We are now beginning to appreciate that intestinal wound repair is regulated, in part, by common receptors expressed on both leukocytes and intestinal epithelial cells (IECs). We recently determined that the ubiquitously expressed membrane protein CD47 is necessary for regulating mucosal wound healing in the intestine and our current data indicates a role for CD47 in both neutrophil (PMN) recruitment and IEC migration. Our preliminary data suggests that CD47-deficient IECs and PMN express less thrombospondin-1 (TSP1), a soluble ligand for CD47, which promotes PMN recruitment to injured mucosa. PMNs, as the first responders, also secrete Leukotriene B4 (LTB4) that binds to its high affinity receptor BLT1 expressed on PMN and amplifies their recruitment. Interestingly, we recently found that IECs also express BLT1 and its ligation by LTB4 promotes mucosal wound repair. In this project, LTB4 and TSP1 are separately evaluated as ligands for receptors expressed on PMNs and IECs during inflammation and repair in the gut. We will build on our preliminary data and previous studies to move toward our goal of understanding mechanisms regulating mucosal wound repair under inflammatory conditions as seen in IBD. These studies will not only shed new light on the complex interplay between inflammatory cells and epithelial cells in orchestrating intestinal mucosal injury/repair in health and disease but may provide new ideas for druggable targets to promote wound repair during mucosal inflammation.

摘要