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Thursday, April 25, 2013
Opening Reception & Poster Session
ABSTRACT FINAL ID: 8
INTERLEUKIN-7 (IL7) AND IL7 RECEPTOR ARE NOVEL MEDIATORS IN THE DEVELOPMENT OF PULMONARY HYPERTESNION IN HUMANS AND MICE
J. Chen, S. Shahrara, A. Yamaura, S.R. Justin, H. Tang, L. Xie, A. Fahs, S. Song, J.G. Garcia, J.X. Yuan, R.F. Machado. University of IL at Chicago, Chicago, IL
Rationale: Interleukin 7 (IL7) stimulates alveolar epithelial cell proliferation and higher levels of IL7/IL7R are associated with decreased survival in lung cancer. We reason that ligation of IL7 to IL7R enhances pulmonary artery smooth muscle cell (PASMC) proliferation by increasing cytosolic calcium concentration ([Ca2+]cyto), which regulates pulmonary vasoconstriction and vascular remodeling.
Methods: IL7 levels from plasma samples (96 PAH patients and 46 controls) were measured using IL7 Bio-plexTM Pro assay (Bio-rad). Lung tissues from three non-PAH controls and three PAH patients and a mouse model of hypoxia-mediated pulmonary hypertension (HPH) were used to study IL7/IL7R mRNA and protein levels by Western blotting and real-time PCR, respectively. IL7R-deficient mice (IL7R-/-) and C57Bl6 wild-type littermates (WT) were exposed to normoxia or 10% FiO2 for four weeks (n=11 per group). Right ventricular systolic pressure (RVSP) was determined with a Millar pressure transducer catheter. The right ventricle: left ventricle +septum (RV/LV+S) ratio was calculated. Pulmonary artery remodeling was assessed using Aperio image software. In a cell culture model, human pulmonary arterial smooth muscle cells (PASMC) were stimulated with recombinant IL7 (10 ng/ml) for 6 and 48 hrs. [Ca2+]cyt was measured in PASMC loaded with flura-2/AM (4 microM) in a fluorescence microscope and cyclepiazonic acid (CPA, a specific Ca2+-ATPase inhibitor) was used to induce store-operated calcium entry (SOCE). A BrDu incorporation assay (CalBiochem) was used to study whether IL7 (10, 50 and 100 ng/ml) treatment for 24 hrs promotes PASMC proliferation.
Results: Plasma IL7, lung IL7/IL7R mRNA and protein levels were significantly elevated in PAH patients and in mouse HPH. Under normoxia RVSP and RV/LV+S did not …
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