2018 • Health Sciences
Nutritional Regulation of Gastrointestinal Inflammatory Responses: A Case for Biogenic Amines
Lead Presenter: Katlynn Gwilt
Additional Presenters: Rachel Hoffing, Neva Olliffe, Gregory Miller
PI: Gregory Miller
Trace amines (TAs), including β-phenylethylamine (PEA) and p-Tyramine, are found in fermented foods including cheese, sausages, and sauerkraut. Aside from the classical “cheese effect” seen in patients consuming TA-rich foods, exacerbated with concomitant use of monoamine-oxidase inhibitors, there are limited studies investigating TAs in human gastrointestinal health. Recently deorphanized TA receptor: Trace Amine Associated Receptor 1 (TAAR1) responds to TAs at nanomolar concentrations. Our previous work identified TAAR1 expression in immune cells and others have demonstrated TAAR1-dependent chemotaxis, cytokine secretion and changes in downstream gene expression after treating immune cells with trace amines. The gastrointestinal tract is home to resident immune cells and nervous tissue and often recruits peripheral blood cells to very closely regulate gastrointestinal homeostasis. Dysregulation of any of these homeostatic mechanisms hallmarks a spectrum of gastrointestinal inflammatory (GI) diseases. Given TAAR1 expression in immune cells and the prevalence for TAs in the western diet which aggravate GI diseases, we are investigating the role of TAAR1 in TA modulation of GI responses by macrophages in human cell lines and in an ex-vivo mouse model comparing wild-type to TAAR1 knockout (TAAR1-/-) phenotypes. Results: 1) activation of human monocytes and mouse bone marrow-derived macrophages (BMDM) with lipopolysaccharide (LPS) upregulates TAAR1 expression; 2) tyramine (1uM) upregulates TAAR1 expression in BMDM; and 3) tyramine (1uM) upregulates proinflammatory cytokine gene expression in BMDM. These responses were absent in TAAR1-/- mice. Establishing TAAR1 as a mediator of GI inflammation induced by dietary TAs may provide a new therapeutic target for treating GI diseases.