Reduction of neutrophilic inflammation in idiopathic pulmonary fibrosis via metabolism of n-alpha-pgp by leukotriene A4 hydrolase
department or school: Medicine, Faculty of
department or school: Medicine, Department of
data provider: DSpace
degree campus: UBCV
creator: Hojabrpour, Payman
issued: 2019-09-30T00:00:00
issued: 2018
related degree: Master of Science - MSc
degree grantor: University of British Columbia
description: Idiopathic Pulmonary Fibrosis (IPF) is a progressive and lethal disease characterized by injury and accumulation of fibroblasts, and abnormal remodeling of the lung parenchyma. IPF is a rare disease with no effective treatment. Due to etiology of IPF, several pathogenic mechanisms have been implicated in its development including: aberrant repair of injured epithelium, consistent fibroblast activation and epithelial-to-mesenchymal transition (EMT). The main focus of this research is on the regulation of a bifunctional enzyme called Leukotriene A4 Hydrolase (LTA4H), with pro and anti-inflammatory functions. While LTA4H catalyzes the conversion of leukotriene A4 to the proinflammatory mediator leukotriene B4 (LTB4), it has an aminopeptidase activity that has shown to degrade N-alpha-Proline-Glycine-Proline (N-α-PGP) and non-acetylated PGP, leading to resolution of acute neutrophils driven inflammation in collagen break down during repair process. Chronic neutrophilic inflammation is observed in lung diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD), mediating extensive tissue damage and contributing to organ dysfunction. These studies demonstrated that tissues and fibroblasts cultured from lungs tissues of IPF patients to contain more PGP content and lack extracellular LTA4H and matrix metalloproteinases 8 and 9 (MMP 8/9). In addition, LTA4H expression was much lower in fibrotic lungs when compared to normal patients. Immunohistochemistry (IHC) analysis of the tissue microarray of the IPF and normal patients indicated a reduction in LTA4H in basal, central and lingual part of the lung. In addition to LTA4H studies, it has been also demonstrated that phosphorylation of the c-Jun N-terminal kinases 1/2(JNK), a mitogen-activated protein kinase family which are responsive to stress stimuli, might be linked to remodelling and progression of the IPF. While the expression of JNK was not different across the IPF and normal patients, activa…
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/67127
note: REDUCTION OF NEUTROPHILIC INFLAMMATION IN IDIOPATHIC PULMONARY FIBROSIS VIA METABOLISM OF N-ALPHA-PGP BY LEUKOTRIENE A4 HYDROLASE by PAYMAN HOJABRPOUR B.Sc., University of British Columbia, 1998 B.IT, Computer Programming, BCIT 2004 A DISSERTATION SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE in THE FACULTY OF GRADUATE AND POST DOCTORAL STUDIES (Experimental Medicine) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) SEPTEMBER 2018 © Payman Hojabrpour, 2018 ii The following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, a thesis/dissertation entitled: submitted by Payman Hojabrpour in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE in Experimental Medicine Examining Committee: Dr. Vincent Duronio Supervisor Dr. Nasreen Khalil Supervisory Committee Member Dr. Michael Cox External Examiner Additional Examiner Additional Supervisory Committee Members: Supervisory Committee Member Supervisory Committee Member iii Abstract Idiopathic Pulmonary Fibrosis (IPF) is a progressive and lethal disease characterized by injury and accumulation of fibroblasts, and abnormal remodeling of the lung parenchyma. IPF is a rare disease with no effective treatment. Due to etiology of IPF, several pathogenic mechanisms have been implicated in its development including: aberrant repair of injured epithelium, consistent fibroblast activation and epithelial-to-mesenchymal transition (EMT). The main focus of this research is on the regulation of a bifunctional enzyme called Leukotriene A4 Hydrolase (LTA4H), with pro and anti-inflammatory functions. While LTA4H catalyzes the conversion of leukotriene A4 to the proinflammatory mediator leukotriene B4 (LTB4), it has an aminopeptidase activity that has shown to degrade N-alpha-Proline-Glycine-Proline (N-α-PGP) and non-acetylated PGP, leading to resolution of acute neutrophils driven inflammation in collagen…
has type: Thesis/Dissertation
date issued: 2018-11
is shown at: 10.14288/1.0371943
language: eng
degree discipline: Experimental Medicine
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivatives 4.0 International
rights URI: http://creativecommons.org/licenses/by-nc-nd/4.0/
scholar level: Graduate
type: Text
identifier URI: http://hdl.handle.net/2429/67127