Immunomodulatory Role of Diet and Adipokines in Multiple Sclerosis and Its Animal Model.

摘要

In this first year of funding we characterized the direct actions of adiponectin on murine T lymphocytes in vitro. Adiponectin induced lymphocyte proliferation in the absence of the specific antigen against which they were activated in vivo (MOG35-55). We will further study the mechanisms leading to these phenomena in the next year by silencing expression of adiponectin receptors on murine T cells. We have also performed experiments an in vitro model of blood brain barrier (BBB). We demonstrated expression of adiponectin receptors on astrocytes and endothelial cells, the two BBB components. Next, we tested adiponectin effects on the BBB. In vitro barrier integrity was assessed by measurement of transendothelial electrical resistance (TEER) or diffusion of fluorescently labeled solutes (fluorescein-dextran). Treatment with adiponectin significantly increases TEER and decreases the diffusivity of fluorescein-dextran compared to treatment with vehicle (PBS). These findings suggest that adiponectin in vitro decreases BBB permeability. No significant effects of adiponectin were observed on level of expression of the endothelial molecules VCAM and VE-cadherin. Furthermore, we have started studying expression of adiponectin receptors on peripheral blood immune cells in MS patients and controls by flow cytometry and on autopsied human MS and non-MS tissues by immunohistochemistry.