title: MUC18 Regulates Lung Rhinovirus Infection and Inflammation.
abstract: BACKGROUND
  MUC18 is upregulated in the lungs of asthma and COPD patients. It has been shown to have pro-inflammatory functions in cultured human airway epithelial cells during viral infections and in mice during lung bacterial infections. However, the in vivo role of MUC18 in the context of viral infections remains poorly understood. The goal of this study is to define the in vivo function of MUC18 during respiratory rhinovirus infection.
  
  
  METHODS
  Muc18 wild-type (WT) and knockout (KO) mice were infected with human rhinovirus 1B (HRV-1B) and sacrificed after 1 day to determine the inflammatory and antiviral responses. To examine the direct effects of Muc18 on viral infection, tracheal epithelial cells isolated from WT and KO mice were grown under air-liquid interface and infected with HRV-1B. Finally, siRNA mediated knockdown of MUC18 was performed in human airway epithelial cells (AECs) to define the impact of MUC18 on human airway response to HRV-1B.
  
  
  RESULTS
  Both viral load and neutrophilic inflammation were significantly decreased in Muc18 KO mice compared to WT mice. In the in vitro setting, viral load was significantly lower and antiviral gene expression was higher in airway epithelial cells of Muc18 KO mice than the WT mice. Furthermore, in MUC18 knockdown human AECs, viral load was decreased and antiviral gene expression was increased compared to controls.
  
  
  CONCLUSIONS
  Our study is the first to demonstrate MUC18's pro-inflammatory and pro-viral function in an in vivo mouse model of rhinovirus infection.
authors.affiliation: Department of Medicine, National Jewish Health, 1400 Jackson Street, Denver, Colorado 80206, United States of America.
authors.forename: Reena
authors.initials: R
authors.lastname: Berman
authors.affiliation: Department of Medicine, National Jewish Health, 1400 Jackson Street, Denver, Colorado 80206, United States of America.
authors.forename: Di
authors.initials: D
authors.lastname: Jiang
authors.affiliation: Department of Medicine, National Jewish Health, 1400 Jackson Street, Denver, Colorado 80206, United States of America.
authors.forename: Qun
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Medicine, National Jewish Health, 1400 Jackson Street, Denver, Colorado 80206, United States of America.
authors.forename: Connor R
authors.initials: CR
authors.lastname: Stevenson
authors.affiliation: Department of Medicine, National Jewish Health, 1400 Jackson Street, Denver, Colorado 80206, United States of America.
authors.forename: Niccolette R
authors.initials: NR
authors.lastname: Schaefer
authors.affiliation: Department of Medicine, National Jewish Health, 1400 Jackson Street, Denver, Colorado 80206, United States of America.
authors.forename: Hong Wei
authors.initials: HW
authors.lastname: Chu
mesh_terms: D000818:Animals; D051929:CD146 Antigen / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism / Q000821:virology; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D010850:Picornaviridae Infections / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D012229:Rhinovirus / Q000502:physiology*; D014132:Trachea / Q000166:cytology / Q000378:metabolism / Q000821:virology; D019562:Viral Load
chemical_list: D051929:CD146 Antigen; C497902:MCAM protein, human; C497903:Mcam protein, mouse