Date Approved

12-2012

Graduate Degree Type

Thesis

Degree Name

Biomedical Sciences (M.H.S.)

Degree Program

Biomedical Sciences

Abstract

Eotaxin is a potent chemoattractant for eosinophils that becomes elevated in the tissues in response to inflammation and increased adiposity. Therefore, eosinophil migration into adipose tissue should increase in diet-induced obese individuals, yet it does not. This suggested to us that something within the cellular microenvironment of diet-induced obese individuals might be altering the endothelial leukocyte adhesion molecules (ELAM) such as VCAM-1 or selectins on the endothelial cells, thus preventing eosinophils from entering the inflamed tissue. Connexons are gap junctions in endothelial cells and on immune cells such as macrophages that are composed of connexins and have been shown to alter ELAM expression. In this study, we investigated whether connexin 43 expression can be modulated by saturated or unsaturated fatty acids. We found that the saturated fatty acids, palmitic and lauric acid, increased expression of connexin 43 in bEnd.3 endothelial cells over a 24-hour period at concentrations ranging from 100μM to 400μM. Conversely, linoleic acid, an unsaturated fatty acid, decreased the expression of connexin 43 over a 24-hour period at concentrations from 400μM to 800μM. Connexins 37 and 40 were also examined but were not detected under the conditions used. These results suggest that the concentration and type of fatty acids in the blood can significantly impact connexin expression by vascular endothelial cells and the subsequent regulation of adhesion molecule expression necessary for eosinophil migration into inflamed tissues.

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