title: Rhinovirus infection and house dust mite exposure synergize in inducing bronchial epithelial cell interleukin-8 release.
abstract: BACKGROUND
  Human rhinoviruses (HRVs) and house dust mites (HDMs) are among the most common environmental factors able to induce airway inflammation in asthma. Although epidemiological studies suggest that they also synergize in inducing asthma exacerbations, there is no experimental evidence to support this, nor any information on the possible mechanisms involved.
  
  
  OBJECTIVE
  To investigate their interaction on the induction of airway epithelial inflammatory responses in vitro.
  
  
  METHODS
  BEAS-2B cells were exposed to activated HDM Dermatophagoides pteronyssinus major allergen I (Der p I), HRVs (HRV1b or HRV16) or both in different sequences. IL-8/CXCL8 release, intercellular adhesion molecule (ICAM)-1 surface expression and nuclear factor kappaB (NF-kappaB) translocation were evaluated. Complementary, primary human bronchial epithelial cells (HBECs) exposed to both Der p I and RVs and IL-8, IL-6, IFN-gamma-induced protein (IP)-10/CXCL10, IFN-lambda1/IL-29, regulated upon activation normal T lymphocyte expressed and secreted (RANTES)/CCL5 release were measured.
  
  
  RESULTS
  RV and Der p I up-regulated IL-8 release, ICAM-1 expression and NF-kappaB translocation in BEAS-2B cells. Simultaneous exposure to both factors, as well as when cells were initially exposed to HRV and then to Der p I, resulted in further induction of IL-8 in a synergistic manner. Synergism was not observed when cells were initially exposed to Der p I and then to HRV. This was the pattern in ICAM-1 induction although the phenomenon was not synergistic. Concurrent exposure induced an early synergistic NF-kappaB translocation induction, differentiating with time, partly explaining the above observation. In HBECs, both HRV and Der p I induced IL-8, IL-6, IL-29 and IP-10, while RANTES was induced only by HRV. Synergistic induction was observed only in IL-8.
  
  
  CONCLUSIONS
  HRV and enzymatically active Der p I can act synergistically in the induction of bronchial epithelial IL-8 release, when HRV infection precedes or is concurrent with Der p I exposure. Such a synergy may represent an important mechanism in virus-induced asthma exacerbations.
authors.affiliation: Allergy Department, 2nd Pediatric Clinic, University of Athens, Athens, Greece. apostolos.bossios@gu.se
authors.forename: A
authors.initials: A
authors.lastname: Bossios
authors.forename: D
authors.initials: D
authors.lastname: Gourgiotis
authors.forename: C L
authors.initials: CL
authors.lastname: Skevaki
authors.forename: P
authors.initials: P
authors.lastname: Saxoni-Papageorgiou
authors.forename: J
authors.initials: J
authors.lastname: Lötvall
authors.forename: S
authors.initials: S
authors.lastname: Psarras
authors.forename: T
authors.initials: T
authors.lastname: Karpathios
authors.forename: A G
authors.initials: AG
authors.lastname: Constandopoulos
authors.forename: S L
authors.initials: SL
authors.lastname: Johnston
authors.forename: N G
authors.initials: NG
authors.lastname: Papadopoulos
mesh_terms: D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D060829:Arthropod Proteins; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000187:drug effects; D002460:Cell Line; D003546:Cysteine Endopeptidases; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects / Q000276:immunology; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D010850:Picornaviridae Infections / Q000276:immunology*; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000187:drug effects; D039981:Pyroglyphidae / Q000276:immunology*; D012229:Rhinovirus / Q000276:immunology*; D014779:Virus Replication / Q000187:drug effects; D000097782:NF-kappaB-Inducing Kinase
chemical_list: D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D015815:Cell Adhesion Molecules; D003546:Cysteine Endopeptidases; D016207:Cytokines; D016209:Interleukin-8; D017346:Protein Serine-Threonine Kinases; D000097782:NF-kappaB-Inducing Kinase; C451162:Dermatophagoides pteronyssinus antigen p 1