Folate Receptor Positive Adipose Tissue Macrophages and EC0746, a Folate Conjugated Anti-Inflammatory Drug

Since type 2 diabetes is associated with inflammation and EC0746 (folate-targeted aminopterin) can treat inflammatory diseases the goal of this thesis was to determine whether EC0746 could ameliorate the symptoms of type 2 diabetes. This thesis successfully analyzes the adipose tissue macrophage (ATM) and determined that it expressed a functional folate receptor (FR) that not only was active but could be targeted with folate conjugates. This thesis also describes the experimental treatment of EC0746 on diabetic mice. Unfortunately, no significant effect was determined and therefore a more thorough study of the FR+ ATMs and EC0746 was performed. The FR+ ATMs were classified as being in a transition state with high expression levels for both a pro- and anti-inflammatory marker. This thesis further details that EC0746 does not inhibit the chemotaxis or cytokine production of human blood monocytes. EC0746 did however affect the recruitment of precursor cells and macrophages to sites of inflammation. This work also demonstrates that obesity appears to suppress FR expression on ATMs and impedes the recruitment of inflammatory cells