Browsing by Author "Flores, Sarah"

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    Activation of Dendritic Cells by Soypeptide Lunasin: Implication in Vaccine Adjuvant
    (Office of the Vice Chancellor for Research, 2014-04-11) Flores, Sarah; Dong, Melissa; Tung, Chun-Yu; Chang, Hua-Chen
    Adjuvants enhance the immunogenicity of vaccines and improve the immune responses. Although many adjuvants are currently used in research, FDA approved aluminum salt (Alum) remains the most often used in human vaccines. Alum is known to promote the Th2 immune response and enhance antibody production, but is less efficient on eliciting Th1 and CTL cellular responses. Thus, it is prudent to improve the effectiveness of current adjuvants or to develop a novel alternative adjuvant. We have recently identified lunasin, a seed peptide from soybeans, as a novel immune modulator. The objective is to define the effectiveness of lunasin peptide as an adjuvant that can enhance the protective immunity of vaccines. Our studies have revealed stimulatory effects of lunasin on dendritic cells (DCs) by regulating expression of a number of genes that are important for immune responses. Lunasin-treated human conventional DCs (cDCs) not only expressed elevated levels of co-stimulatory molecules (CD86) but also exhibited up-regulation of chemokines (CCL2, CCL3, CCL4) and cytokine (IL-1β). To determine the function of lunasin-treated cDCs, these cells were co-cultured with allogeneic human peripheral blood CD4+ T cells for 7 days in the mixed lymphocyte reaction. Lunasin-treated cDCs induced almost 2-fold higher proliferation of allogeneic CD4+ T cells when comparing with a sham treatment. To verify the in vivo effects, lunasin was administered into mice. Increased CD86 expression was found in cDCs from spleens of mice treated with lunasin. Furthermore, mice vaccinated with lunasin-adjuvanted ovalbumin (OVA) had reduced tumor growth following challenging with OVA-expressing A20 B-lymphoma cells. Taken together, our data suggest that lunasin may act as a vaccine adjuvant by targeting DCs to enhance and modulate the immune responses to antigens.
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    Mechanisms underlying capsaicin effects in canine coronary artery: implications for coronary spasm
    (Oxford University Press, 2014-09-01) Hiett, S. Christopher; Owen, Meredith K.; Li, Wennan; Chen, Xingjuan; Riley, Ashley; Noblet, Jillian; Flores, Sarah; Sturek, Michael; Tune, Johnathan D.; Obukhov, Alexander G.; Department of Cellular & Integrative Physiology, IU School of Medicine
    AIMS: The TRPV1, transient receptor potential vanilloid type 1, agonist capsaicin is considered to be beneficial for cardiovascular health because it dilates coronary arteries through an endothelial-dependent mechanism and may slow atheroma progression. However, recent reports indicate that high doses of capsaicin may constrict coronary arterioles and even provoke myocardial infarction. Thus far, the mechanisms by which TRPV1 activation modulates coronary vascular tone remain poorly understood. This investigation examined whether there is a synergistic interplay between locally acting vasoconstrictive pro-inflammatory hormones (autacoids) and capsaicin effects in the coronary circulation. METHODS AND RESULTS: Experiments were performed in canine conduit coronary artery rings and isolated smooth muscle cells (CASMCs). Isometric tension measurements revealed that 1-10 μM capsaicin alone did not affect resting tension of coronary artery rings. In contrast, in endothelium-intact rings pre-contracted with a Gq/11-coupled FP/TP (prostaglandin F/thromboxane) receptor agonist, prostaglandin F2α (PGF2α; 10 μM), capsaicin first induced transient dilation that was followed by sustained contraction. In endothelium-denuded rings pre-contracted with PGF2α or thromboxane analogue U46619 (1 μM, a TP receptor agonist), capsaicin induced only sustained contraction. Blockers of the TP receptor or TRPV1 significantly inhibited capsaicin effects, but these were still observed in the presence of 50 μM nifedipine and 70 mM KCl. Capsaicin also potentiated 20 mM KCl-induced contractions. Fluorescence imaging experiments in CASMCs revealed that the Gq/11-phospholipase C (PLC)-protein kinase C (PKC) and Ca(2+)-PLC-PKC pathways are likely involved in sensitizing CASMC TRPV1 channels. CONCLUSION: Capsaicin alone does not cause contractions in conduit canine coronary artery; however, pre-treatment with pro-inflammatory prostaglandin-thromboxane agonists may unmask capsaicin's vasoconstrictive potential.