Dr. Dorothy M. Ainsworth
In this proposal we will test the hypothesis that genistein and luteolin, two bioflavonoids, attenuate pulmonary mononuclear cell production of inflammatory cytokines. The 1 st specific aim will optimize the dosage of genistein and of luteolin needed to inhibit the production of IL-8, IL-6, TNF-a and IL-1ß in cultured, haydust-stimulated pulmonary mononuclear cells. Cells would be isolated from young adult horses that have been maintained on pasture for 2 months. The 2 nd aim will determine if prior stabling (exposure to haydust) increases the dosage of either flavonoid required to inhibit cytokine transcription in cultured, haydust-stimulated pulmonary mononuclear cells. Cells would be isolated from horses that had been stabled for 1 month and fed high quality alfalfa hay. In both aims, gene transcription would be measured using real time PCR; flavonoid-induced inhibition of NF-?B (p65 subunit) would be measured by ELISA and flavonoid-induced cytotoxcity would be assessed by cell viability staining (trypan blue).
The long-term goal is to determine if dietary supplementation of flavonoids protects against the development of IAD. Ultimately the results of the current study will add to our understanding of the equine inflammatory process. The results also have direct applicability to disorders affecting the gastrointestinal as well as the musculoskeletal systems.