Browsing by Author "Dave, Priya"

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    Cardiac and Skeletal Muscle Lipotoxicity in a Rat Model of Pulmonary Arterial Hypertension
    (Office of the Vice Chancellor for Research, 2015-04-17) Dave, Priya; Cooney, Sean; Lahm, Tim; Brown, Mary Beth
    Patients with Pulmonary Arterial Hypertension (PAH)experience shift from aerobic to anaerobic respiration in cardiac and skeletal muscle myocytes. This shift can be identified histologically by an increased presence of the glucose transporter Glut 1 in the tissue, indicating increased reliance on cytoplasmic glycolysis. Previous studies have demonstrated that in patients with diabetes, an increase in Glut 1 is accompanied by an increase in fat storage in the cell. Excessive myocyte fat storage may contribute to tissue and systemic inflammation and has therefore been termed ‘lipotoxicity’. This study tested the hypothesis in a PAH rat model that an increase in cardiac and skeletal muscle Glut 1 abundance would be associated with an increase in fat storage in the cell. Oil Red O staining was performed to assay for lipotoxicity in cryosections of right ventricle and soleus muscle tissue, imaged using brightfield microscopy. The experiment was conducted using tissue from a moderately severe PAH phenotype produced by monocrotaline(60 mg/kg) injection, as well as from saline injected control animals. Lipids have been observed in the first few samples tested with Oil Red O staining, and results are still pending as a larger sample size is currently being collected.
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    Ex vivo culture of mouse skin activates an interleukin 1 alpha-dependent inflammatory response
    (Wiley, 2020-01) Zhou, Hong-Ming; Slominski, Radomir M.; Seymour, Leroy J.; Bell, Maria C.; Dave, Priya; Atumonye, Joseph; Wright, William, III.; Dawes, Avery; Griesenauer, Brad; Paczesny, Sophie; Kaplan, Mark H.; Spandau, Dan F.; Turner, Matthew J.; Dermatology, School of Medicine
    Ex vivo culture of mouse and human skin causes an inflammatory response characterized by production of multiple cytokines. We used ex vivo culture of mouse tail skin specimens to investigate mechanisms of this skin culture-induced inflammatory response. Multiplex assays revealed production of interleukin 1 alpha (IL-1α), interleukin 1 beta (IL-1β), interleukin 6 (IL-6), chemokine C-X-C motif ligand 1 (CXCL1), granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) during skin culture, and quantitative PCR revealed transcripts for these proteins were also increased. Ex vivo cultures of skin from myeloid differentiation primary response 88 deficient mice (Myd88-/- ) demonstrated significantly reduced expression of transcripts for the aforementioned cytokines. The same result was observed with skin from interleukin 1 receptor type 1 deficient mice (Il1r1-/- ). These data suggested the IL-1R1/MyD88 axis is required for the skin culture-induced inflammatory response and led us to investigate the role of IL-1α and IL-1β (the ligands for IL-1R1) in this process. Addition of IL-1α neutralizing antibody to skin cultures significantly reduced expression of Cxcl1, Il6 and Csf3. IL-1β neutralization did not reduce levels of these transcripts. These studies suggest that IL-1α promotes the skin the culture-induced inflammatory response.