Harnessing Eosinophils as a Potential Tumoricidal Immunotherapy

Eosinophils have numerous functions for defense against pathogens, despite being only 1-5% of total circulating blood leukocytes. Most well known for their actions contributing to asthma and allergic disease, eosinophils are thought to have homeostatic roles in the thymus, uterus, mammary glands, and gut. Furthermore, recent studies have also indicated a role for eosinophils as sentinels of tumorigenesis (2-6). Our studies show that eosinophils can elicit tumoricidal activity in a dose dependent manner against a variety of cancer cells. We also attempted to optimize the cytotoxicity of eosinophils by activating different receptors. We were able to verify different methods to stimulate eosinophil activation, including incubation with cytokines, especially granulocyte macrophage, colony stimulating factor (GM-CSF), and crosslinking the FcαR. Eosinophils do have tumoricidal activity, but further research is needed to both understand this interaction and to optimize the eosinophil’s tumoricidal properties

Naringenin inhibits adipogenesis and reduces insulin sensitivity and adiponectin expression in adipocytes

Adipose tissue development and function are widely studied to examine the relationship between obesity and the metabolic syndrome. It is well documented that the inability of adipose tissue to properly increase its lipid storage capacity during the obese state can lead to metabolic dysfunction. In a blind screen of 425 botanicals, we identified naringenin as an inhibitor of adipocyte differentiation. Naringenin is one of the most abundant citrus flavonoids, and recent studies have demonstrated antihyperlipidemic capabilities. These studies have largely focused on the effects of naringenin on the liver. Our biochemical studies clearly demonstrate that naringenin inhibits adipogenesis and impairs mature fat cell function. Naringenin specifically inhibited adipogenesis in a dose-dependent fashion as judged by examining lipid accumulation and induction of adipocyte marker protein expression. In mature 3T3-L1 adipocytes, naringenin reduced the ability of insulin to induce IRS-1 tyrosine phosphorylation and substantially inhibited insulin-stimulated glucose uptake in a dose-dependent manner and over a time frame of 1.5 to 24 hours. Exposure to naringenin also inhibited adiponectin protein expression in mature murine and human adipocytes. Our studies have revealed that naringenin may have a negative impact on adipocyte-related diseases by limiting differentiation of preadipocytes, by significantly inducing insulin resistance, and by decreasing adiponectin expression in mature fat cells. © 2013 Allison J. Richard et al