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Browsing by Author "Department of Oral Pathology, Medicine and Radiology, IU School of Dentistry"
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Item Functional characterization of a competitive peptide antagonist of p65 in human macrophage-like cells suggests therapeutic potential for chronic inflammation(Dove Medical Press, 2014) Srinivasan, Mythily; Blackburn, Corinne; Lahiri, Debomoy K.; Department of Oral Pathology, Medicine and Radiology, IU School of DentistryGlucocorticoid-induced leucine zipper (GILZ) is a glucocorticoid responsive protein that links the nuclear factor-kappa B (NFκB) and the glucocorticoid signaling pathways. Functional and binding studies suggest that the proline-rich region at the carboxy terminus of GILZ binds the p65 subunit of NFκB and suppresses the immunoinflammatory response. A widely-used strategy in the discovery of peptide drugs involves exploitation of the complementary surfaces of naturally occurring binding partners. Previously, we observed that a synthetic peptide (GILZ-P) derived from the proline-rich region of GILZ bound activated p65 and ameliorated experimental encephalomyelitis. Here we characterize the secondary structure of GILZ-P by circular dichroic analysis. GILZ-P adopts an extended polyproline type II helical conformation consistent with the structural conformation commonly observed in interfaces of transient intermolecular interactions. To determine the potential application of GILZ-P in humans, we evaluated the toxicity and efficacy of the peptide drug in mature human macrophage-like THP-1 cells. Treatment with GILZ-P at a wide range of concentrations commonly used for peptide drugs was nontoxic as determined by cell viability and apoptosis assays. Functionally, GILZ-P suppressed proliferation and glutamate secretion by activated macrophages by inhibiting nuclear translocation of p65. Collectively, our data suggest that the GILZ-P has therapeutic potential in chronic CNS diseases where persistent inflammation leads to neurodegeneration such as multiple sclerosis and Alzheimer's disease.Item Insight into the pathogenesis and nature of Central Giant Cell Lesions of the Jaws(Medicina Oral S.L., 2015-03-01) Edwards, Paul C.; Department of Oral Pathology, Medicine and Radiology, IU School of DentistryCentral giant cell lesions of the jaws are not uncommon. While the majority of these represent single, sporadic lesions, histologically identical lesions are seen in association with a number of other bone lesions, as well as in certain syndromes. This manuscript offers a brief update on recent developments in this area that provide new insight into the pathogenesis and nature of Central Giant Cell Lesions of the Jaws.