title: Rhinovirus infection induces extracellular matrix protein deposition in asthmatic and nonasthmatic airway smooth muscle cells.
abstract: Airway remodeling, which includes increases in the extracellular matrix (ECM), is a characteristic feature of asthma and is correlated to disease severity. Rhinovirus (RV) infections are associated with increased risk of asthma development in young children and are the most common cause of asthma exacerbations. We examined whether viral infections can increase ECM deposition and whether this increased ECM modulates cell proliferation and migration. RV infection of nonasthmatic airway smooth muscle (ASM) cells significantly increased the deposition of fibronectin (40% increase, n = 12) and perlecan (80% increase, n = 14), while infection of asthmatic ASM cells significantly increased fibronectin (75% increase, n = 9) and collagen IV (15% increase, n = 9). We then treated the ASM cells with the Toll-like receptor (TLR) agonists polyinosinic:polycytidylic acid, imiquimod, and pure RV RNA and were able to show that the mechanism through which RV induced ECM deposition was via the activation of TLR3 and TLR7/8. Finally, we assessed whether the virus-induced ECM was bioactive by measuring the amount of migration and proliferation of virus-naive cells that seeded onto the ECM. Basically, ECM from asthmatic ASM cells induced twofold greater migration of virus-naive ASM cells than ECM from nonasthmatic ASM cells, and these rates of migration were further increased on RV-modulated ECM. Increased migration on the RV-modulated ECM was not due to increased cell proliferation, as RV-modulated ECM decreased the proliferation of virus-naive cells. Our results suggest that viruses may contribute to airway remodeling through increased ECM deposition, which in turn may contribute to increased ASM mass via increased cell migration.
authors: Discipline of Pharmacology, University of Sydney, Camperdown, Australia.
authors: Curtis
authors: C
authors: Kuo
authors: Sam
authors: S
authors: Lim
authors: Nicholas J C
authors: NJ
authors: King
authors: Sebastian L
authors: SL
authors: Johnston
authors: Janette K
authors: JK
authors: Burgess
authors: Judith L
authors: JL
authors: Black
authors: Brian G
authors: BG
authors: Oliver
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D056151:Airway Remodeling; D001249:Asthma / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D015153:Blotting, Western; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D004279:DNA, Viral / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D010850:Picornaviridae Infections / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D012333:RNA, Messenger / Q000235:genetics; D012137:Respiratory System / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012229:Rhinovirus / Q000502:physiology*; D055815:Young Adult
chemical_list: D004279:DNA, Viral; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D012333:RNA, Messenger