Idiopathic Pulmonary Fibrosis (IPF) is a lethal lung disease with progressive fibrosis and death within 2-3 years of diagnosis. IPF incidence and prevalence rates are increasing annually, and because the pathogenesis is unknown, there are no effective treatments available. Inhibition of interleukin 6 (IL-6) results in the attenuation of pulmonary fibrosis in mice. It is unclear whether this is due to blockade of classical signaling, mediated by membrane-bound IL-6 receptor alpha (mIL-6Rα), or trans signaling, mediated by soluble IL-6Rα (sIL-6Rα). Our study assessed the role of sL-6Rα in IPF. We demonstrated elevations of sIL-6Rα in IPF patients and in mice during the onset and progression of fibrosis and showed that protease-mediated cleavage was important in production of sL-6Rα in fibrotic lungs. In vivo neutralization of sIL-6Rα, and resulting antagonism of IL-6 trans signaling, attenuated pulmonary fibrosis in mice. Decreases in sIL-6Rα were associated with reductions in myofibroblasts, fibronectin and collagen. In vitro activation of IL-6 trans signaling enhanced fibroblast proliferation and extracellular matrix protein production, effects relevant in the progression of pulmonary fibrosis. These findings suggest that IL-6 trans signaling influences events crucial in pulmonary fibrosis in vivo.
","abstract_html":"<p>Idiopathic Pulmonary Fibrosis (IPF) is a lethal lung disease with progressive fibrosis and death within 2-3 years of diagnosis. IPF incidence and prevalence rates are increasing annually, and because the pathogenesis is unknown, there are no effective treatments available. Inhibition of interleukin 6 (IL-6) results in the attenuation of pulmonary fibrosis in mice. It is unclear whether this is due to blockade of classical<em> </em>signaling, mediated by membrane-bound IL-6 receptor alpha (mIL-6Rα), or trans signaling, mediated by soluble IL-6Rα (sIL-6Rα). Our study assessed the role of sL-6Rα in IPF. We demonstrated elevations of sIL-6Rα in IPF patients and in mice during the onset and progression of fibrosis and showed that protease-mediated cleavage was important in production of sL-6Rα in fibrotic lungs. <em>In vivo</em> neutralization of sIL-6Rα, and resulting antagonism of IL-6 trans signaling, attenuated pulmonary fibrosis in mice. Decreases in sIL-6Rα were associated with reductions in myofibroblasts, fibronectin and collagen. <em>In vitro</em> activation of IL-6 trans signaling enhanced fibroblast proliferation and extracellular matrix protein production, effects relevant in the progression of pulmonary fibrosis. These findings suggest that IL-6 trans signaling influences events crucial in pulmonary fibrosis <em>in vivo</em>.</p>","abstract_has_math":false,"creators":["Le, Thuy T"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation (PhD)","degree_discipline":null,"degree_department":null,"school":null,"contributors":["Michael R. Blackburn","Russell Broaddus","Sandeep Agarwal"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2014,"date_issued":"2014-05-01T07:00:00Z","date_published":"2014-05-01T07:00:00Z","updated_at":"2026-07-24T05:50:38Z","subjects":["interleukin 6 trans signaling","soluble IL-6R alpha","idiopathic pulmonary fibrosis","ADAM17","gp130Fc","phospho-STAT3","Medicine and Health Sciences"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://digitalcommons.library.tmc.edu/utgsbs_dissertations/469","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Michael R. Blackburn","Russell Broaddus","Sandeep Agarwal"]},{"key":"dc:creator","label":"Author","values":["Le, Thuy T"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2014-11-07T08:00:00Z"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation (PhD)"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["interleukin 6 trans signaling","soluble IL-6R alpha","idiopathic pulmonary fibrosis","ADAM17","gp130Fc","phospho-STAT3","Medicine and Health Sciences"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://digitalcommons.library.tmc.edu/utgsbs_dissertations/469"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Idiopathic Pulmonary Fibrosis (IPF) is a lethal lung disease with progressive fibrosis and death within 2-3 years of diagnosis. IPF incidence and prevalence rates are increasing annually, and because the pathogenesis is unknown, there are no effective treatments available. Inhibition of interleukin 6 (IL-6) results in the attenuation of pulmonary fibrosis in mice. It is unclear whether this is due to blockade of classical signaling, mediated by membrane-bound IL-6 receptor alpha (mIL-6Rα), or trans signaling, mediated by soluble IL-6Rα (sIL-6Rα). Our study assessed the role of sL-6Rα in IPF. We demonstrated elevations of sIL-6Rα in IPF patients and in mice during the onset and progression of fibrosis and showed that protease-mediated cleavage was important in production of sL-6Rα in fibrotic lungs. In vivo neutralization of sIL-6Rα, and resulting antagonism of IL-6 trans signaling, attenuated pulmonary fibrosis in mice. Decreases in sIL-6Rα were associated with reductions in myofibroblasts, fibronectin and collagen. In vitro activation of IL-6 trans signaling enhanced fibroblast proliferation and extracellular matrix protein production, effects relevant in the progression of pulmonary fibrosis. These findings suggest that IL-6 trans signaling influences events crucial in pulmonary fibrosis in vivo.
"]},{"key":"dc:title","label":"Title","values":["Contribution of Interleukin 6 Trans Signaling In Pulmonary Fibrosis"]}]}],"canonical_facts":{"dc:contributor":["Michael R. Blackburn","Russell Broaddus","Sandeep Agarwal"],"dc:creator":["Le, Thuy T"],"dc:date.available":["2014-11-07T08:00:00Z"],"dc:description.abstract":["Idiopathic Pulmonary Fibrosis (IPF) is a lethal lung disease with progressive fibrosis and death within 2-3 years of diagnosis. IPF incidence and prevalence rates are increasing annually, and because the pathogenesis is unknown, there are no effective treatments available. Inhibition of interleukin 6 (IL-6) results in the attenuation of pulmonary fibrosis in mice. It is unclear whether this is due to blockade of classical signaling, mediated by membrane-bound IL-6 receptor alpha (mIL-6Rα), or trans signaling, mediated by soluble IL-6Rα (sIL-6Rα). Our study assessed the role of sL-6Rα in IPF. We demonstrated elevations of sIL-6Rα in IPF patients and in mice during the onset and progression of fibrosis and showed that protease-mediated cleavage was important in production of sL-6Rα in fibrotic lungs. In vivo neutralization of sIL-6Rα, and resulting antagonism of IL-6 trans signaling, attenuated pulmonary fibrosis in mice. Decreases in sIL-6Rα were associated with reductions in myofibroblasts, fibronectin and collagen. In vitro activation of IL-6 trans signaling enhanced fibroblast proliferation and extracellular matrix protein production, effects relevant in the progression of pulmonary fibrosis. These findings suggest that IL-6 trans signaling influences events crucial in pulmonary fibrosis in vivo.
"],"dc:identifier":["https://digitalcommons.library.tmc.edu/utgsbs_dissertations/469"],"dc:subject":["interleukin 6 trans signaling","soluble IL-6R alpha","idiopathic pulmonary fibrosis","ADAM17","gp130Fc","phospho-STAT3","Medicine and Health Sciences"],"dc:title":["Contribution of Interleukin 6 Trans Signaling In Pulmonary Fibrosis"],"thesis:degree_level":["Dissertation (PhD)"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T05:50:38Z"}