Browsing by Subject "Human Umbilical Vein Endothelial Cells"

Now showing 1 - 3 of 3
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    The first synthesis of the antiangiogenic homoisoflavanone, cremastranone
    (Royal Society of Chemistry, 2014-10-21) Lee, Bit; Basavarajappa, Halesha D.; Sulaiman, Rania S.; Fei, Xiang; Seo, Seung-Yong; Corson, Timothy W.; Department of Ophthalmology, IU School of Medicine
    An antiangiogenic homoisoflavanone, cremastranone, was synthesized for the first time. This scalable synthesis, which includes selective demethylation, could be used to develop lead molecules to treat angiogenesis-induced eye diseases. Synthetic cremastranone inhibited the proliferation, migration and tube formation ability of human retinal microvascular endothelial cells, important steps in pathological angiogenesis.
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    INTERACTIONS OF HUMAN UMBILICAL VEIN ENDOTHELIAL CELLS WITH TOBACCO TREATED STREPTOCOCCUS MUTANS
    (Office of the Vice Chancellor for Research, 2013-04-05) Lanier, Branden; Windsor, L. Jack; Gregory, Richard L.
    Streptococcus mutans and tobacco are risk factors for atherosclerosis. The objective of this study was to determine the ability that a spaP isogenic defective mutant of S. mutans UA 159 has on binding to Human Umbilical Vein Endothelial Cells (HUVEC) when treated with tobacco products and what second messenger signals are involved. The study was conducted to examine the effects that various concentrations of cigarette smoke condensate (CSC)- and nicotine have on S. mutans cell cytotoxicity and expression of cytokines and growth factors from HUVECs. S. mutans was grown at 37°C and planktonic and biofilm cells were separated from the culture supernatant. The supernatant was discarded the cells were washed, sterilized with formaldehyde and washed again to remove the formaldehyde. The concentrations of the various S. mutans cells were standardized to the same concentration (absorbance of 0.50 ± 0.01) by spectroscopy at a wavelength of 600 nm. The lowest non-toxic levels of the sterilized bacterial cells were used to treat HUVECs for 72 hours and cytotoxicity was determined by lactate dehydrogenase (LDH) assays. The cytokine/growth factor expression will be determined by antibody protein arrays. The results are expected to indicate an increase in cytotoxicity with increasing cell concentrations, along with increased pro-inflammatory cytokine/growth factors expression by the HUVECs treated with tobacco treated S. mutans compared to S. mutans that was not treated with tobacco products. Second messenger signaling pathways will be analyzed with ERK and JNK inhibitors and specific antibodies to ERK and phospho-JNK. Immunoblots using HUVECs will be done to determine expression of ERK/JNK. A better understanding of the detrimental effects that tobacco has on the underlining causes of atherosclerosis can advance the quest of controlling the disease.
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    The small GTPase Rap1b negatively regulates neutrophil chemotaxis and transcellular diapedesis by inhibiting Akt activation
    (Rockefeller University Press, 2014-08-25) Kumar, Sachin; Xu, Juying; Kumar, Rupali Sani; Lakshmikanthan, Sribalaji; Kapur, Reuben; Kofron, Matthew; Chrzanowska-Wodnicka, Magdalena; Filippi, Marie-Dominique; Department of Pediatrics, IU School of Medicine
    Neutrophils are the first line of cellular defense in response to infections and inflammatory injuries. However, neutrophil activation and accumulation into tissues trigger tissue damage due to release of a plethora of toxic oxidants and proteases, a cause of acute lung injury (ALI). Despite its clinical importance, the molecular regulation of neutrophil migration is poorly understood. The small GTPase Rap1b is generally viewed as a positive regulator of immune cell functions by controlling bidirectional integrin signaling. However, we found that Rap1b-deficient mice exhibited enhanced neutrophil recruitment to inflamed lungs and enhanced susceptibility to endotoxin shock. Unexpectedly, Rap1b deficiency promoted the transcellular route of diapedesis through endothelial cell. Increased transcellular migration of Rap1b-deficient neutrophils in vitro was selectively mediated by enhanced PI3K-Akt activation and invadopodia-like protrusions. Akt inhibition in vivo suppressed excessive Rap1b-deficient neutrophil migration and associated endotoxin shock. The inhibitory action of Rap1b on PI3K signaling may be mediated by activation of phosphatase SHP-1. Thus, this study reveals an unexpected role for Rap1b as a key suppressor of neutrophil migration and lung inflammation.