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Investigating the role of Splunc1 in the cardio-pulmonary system

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Item Summary

Title: Investigating the role of Splunc1 in the cardio-pulmonary system
Authors: Schorlemmer, Anita
Keywords: Splunc1
Issue Date: Aug 2012
Publisher: [Honolulu] : [University of Hawaii at Manoa], [August 2012]
Abstract: Short Palate Lung and Nasal Epithelial Clone (Splunc1), a protein abundantly expressed in the airways, has been predicted to exert a protective role in the stressed lung. Preliminary data from or laboratory suggested that Splunc1 might also have a protective role in the heart during cardiac stress. We first aimed to confirm a role of Splunc1 in the heart by assessing its expression in various models of cardiac stress in vitro and in vivo. Next, we investigated the role of Splunc1 produced by cardiomyocytes during cardiac stress induced by isoproterenol or methamphetamine exposure, using a conditional cardiomyocyte-specific Splunc1 KO mouse model. Finally, we aimed to elucidate mechanistic details of the protective role of Splunc1 in stressed lungs and developed a systemic Splunc1 KO mouse model. To simulate bacterial airway infections, agonists for Toll-like receptors 2 (TLR-2) and 4 (TLR-4) were instilled into the lungs of Splunc1 KO mice and the inflammatory responses evaluated. A role of Splunc1 in the heart during cardiac stress was not confirmed. The lack of Splunc1 in TLR-2 and TLR-4 stimulation did not affect levels of airway cytokines and chemokines. However, Splunc1 affected the chemotaxis of immune cells into the affected area. Specifically, infiltration of neutrophils and macrophages was increased in bronchial lavages (BAL) from Splunc1 KO mice. The role of Splunc1 in immunological responses in the lung could be an important aspect of lung diseases that are exacerbated by infections.
Description: Ph.D. University of Hawaii at Manoa 2012.
Includes bibliographical references.
URI/DOI: http://hdl.handle.net/10125/101025
Appears in Collections:Ph.D. - Molecular Biosciences and Bioengineering



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