Falsafi, R.

Hancock, R.

Kicic, Anthony

Stick, S.M.

Turvey, S.E.

Xia, J.

English

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16/05/13 3:11 PMAbstract Central - Abstract Proof PopUpPage 1 of 2http://nacfc2013.abstractcentral.com/abstract?TAG_ACTION=VIEW…LSE&NEXT_PAGE=PROOF_POP&SHOW_RECIEPT=TRUE&BLIND_OVERRIDE=TRUE SUBMITTED ABSTRACT This abstract has been submitted as of the date listed below.IMPORTANT INFORMATIONIf you return the abstract to draft for editing, YOU MUST resubmit it for the abstract to be reviewed. PrintSubmittedon May 16, 01:40 AMfor nacfc2013ProofCONTROL ID: 1724624CONTACT (NAME ONLY): Stephen StickAbstract DetailsPRESENTATION TYPE: PosterCURRENT CATEGORY: NEW THERAPIES, BIOMARKERS & OUTCOME MEASURESKEYWORDS: CFTR-interactions.AWARDS: $500 Stipend for Abstract Presenters in Workshops Outside of North AmericaAbstractTITLE: EPITHELIAL-SPECIFIC TRIGGERS OF NEUTROPHILIC INFLAMAMTION FOLLOWING HUMANRHINOVIRUS (HRV) INFECTION IN CHILDREN WITH CYSTIC FIBROSIS (CF)AUTHORS (LAST NAME, FIRST NAME): Stick, Stephen M.1, 2; Kicic, Anthony 2; Falsafi, Reza 3; Turvey,Stuart E.4; Xia, Jianguo 3; Hancock, Robert 3INSTITUTIONS (ALL): 1. Respiratory Medicine, Princess Margaret Hospital for Children, Subiaco, WA,Australia. 2. AREST CF, Telethon Institute for Child Health Research, Perth, WA, Australia. 3. Centre for Microbial Diseases and Immunity Research, University of British Colombia, Vancouver, BC,Canada. 4. Child and family Research Institute, University of British Colombia, Vancouver, BC, Canada. ABSTRACT BODY: BACKGROUND: Neutrophilic airway inflammation is an early feature of CF lung disease.We have previously demonstrated that 1° CF airway epithelial cells (AEC), have damped IFNβ2 and apoptosisas well as increased viral replication and IL-8 release in response to HRV exposure,compared to controls1.These data suggest dysregulated innate immune responses to this viral pathogen could result in a cycle thatpromotes neutrophilic inflammation. The aim of this study was to characterise epithelial innate immunepathways linked to abnormal CFTR function that when stimulated by viral pathogens, result in pro-neutrophilicinflammatory signals. Specifically our hypothesis was that CFTR mutations cause dysregulation of innateimmune pathways resulting in the stimulation of neutrophilic inflammation upon human rhinoviral (HRV)infection. METHODS: 1° AEC were obtained from 5 children with CF (2M, age 1.97-5.51 years (median 4.2years)) and from 5 healthy children (2M; age 3.23-6.36 years (median 4.9 years)). Established AEC cultureswere then infected with HRV1b (MOI 12) for 24 hours. Cells were collected, RNA extracted and quantifiedusing RNA-seq and gene expression and analysed using a systems biology approach with Innate DB andMetaGEX. RESULTS: As a first step in understanding how genes with altered expression levels in responseto viral infection interrelate functionally, gene ontology (GO) overexpression analysis was performed. Thisrevealed that GO terms related to response to virus, immune response, inflammatory response, response towounding and innate immune response were significantly overexpressed in CF AEC following HRV1binfection. More specifically, > 600 genes within these pathways were found to be differentially expressed.Network analysis was then used to understand how transcriptional changes induced by viral infectioninterrelated with CFTR and inflammation proteins in these pathways as network nodes interconnected byprotein-protein interactions. CONCLUSION: We have identified epithelial specific pathways that can triggerneutrophilic inflammation within identified inflammatory networks with node and bottleneck genes that suggest16/05/13 3:11 PMAbstract Central - Abstract Proof PopUpPage 2 of 2http://nacfc2013.abstractcentral.com/abstract?TAG_ACTION=VIEW…LSE&NEXT_PAGE=PROOF_POP&SHOW_RECIEPT=TRUE&BLIND_OVERRIDE=TRUEnovel "druggable" targets.REFERENCES: 1. Sutanto et al., 2011. Am J Respir Cell Mol Biol 44:761.(No Table Selected)(No Image Selected)ScholarOne Abstracts® (patent #7,257,767 and #7,263,655). © ScholarOne, Inc., 2013. All Rights Reserved.ScholarOne Abstracts and ScholarOne are registered trademarks of ScholarOne, Inc. Follow ScholarOne on TwitterTerms and Conditions of UseProduct version number 4.1.0 (Build 59)Build date May 09, 2013 12:41:51. Server tss1be0014

EPITHELIAL-SPECIFIC TRIGGERS OF NEUTROPHILIC INFLAMMATION FOLLOWING HUMAN RHINOVIRUS (HRV) INFECTION IN CHILDREN WITH CYSTIC FIBROSIS (CF)

https://espace.curtin.edu.au/bitstream/20.500.11937/76859/2/77102.pdf

EPITHELIAL-SPECIFIC TRIGGERS OF NEUTROPHILIC INFLAMMATION FOLLOWING HUMAN RHINOVIRUS (HRV) INFECTION IN CHILDREN WITH CYSTIC FIBROSIS (CF)

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