title: Trappin-2/elafin modulate innate immune responses of human endometrial epithelial cells to PolyI:C.
abstract: BACKGROUND
  Upon viral recognition, innate and adaptive antiviral immune responses are initiated by genital epithelial cells (ECs) to eradicate or contain viral infection. Such responses, however, are often accompanied by inflammation that contributes to acquisition and progression of sexually transmitted infections (STIs). Hence, interventions/factors enhancing antiviral protection while reducing inflammation may prove beneficial in controlling the spread of STIs. Serine antiprotease trappin-2 (Tr) and its cleaved form, elafin (E), are alarm antimicrobials secreted by multiple cells, including genital epithelia.
  
  
  RESULTS
  We investigated whether and how each Tr and E (Tr/E) contribute to antiviral defenses against a synthetic mimic of viral dsRNA, polyinosine-polycytidylic acid (polyI:C) and vesicular stomatitis virus. We show that delivery of a replication-deficient adenovector expressing Tr gene (Ad/Tr) to human endometrial epithelial cells, HEC-1A, resulted in secretion of functional Tr, whereas both Tr/E were detected in response to polyI:C. Moreover, Tr/E were found to significantly reduce viral replication by either acting directly on virus or through enhancing polyI:C-driven antiviral protection. The latter was associated with reduced levels of pro-inflammatory factors IL-8, IL-6, TNFα, lowered expression of RIG-I, MDA5 and attenuated NF-κB activation. Interestingly, enhanced polyI:C-driven antiviral protection of HEC-Ad/Tr cells was partially mediated through IRF3 activation, but not associated with higher induction of IFNβ, suggesting multiple antiviral mechanisms of Tr/E and the involvement of alternative factors or pathways.
  
  
  CONCLUSIONS
  This is the first evidence of both Tr/E altering viral binding/entry, innate recognition and mounting of antiviral and inflammatory responses in genital ECs that could have significant implications for homeostasis of the female genital tract.
authors.affiliation: Department of Pathology & Molecular Medicine, McMaster Immunology Research Centre, Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Anna G
authors.initials: AG
authors.lastname: Drannik
authors.forename: Kakon
authors.initials: K
authors.lastname: Nag
authors.forename: Xiao-Dan
authors.initials: XD
authors.lastname: Yao
authors.forename: Bethany M
authors.initials: BM
authors.lastname: Henrick
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Sallenave
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Rosenthal
mesh_terms: D002460:Cell Line; D053492:Elafin / Q000276:immunology*; D004717:Endometrium / Q000166:cytology* / Q000276:immunology / Q000821:virology; D004847:Epithelial Cells / Q000276:immunology* / Q000821:virology*; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D050838:Interferon Regulatory Factor-3 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D016209:Interleukin-8 / Q000276:immunology; D016328:NF-kappa B / Q000276:immunology; D012367:RNA, Viral / Q000737:chemistry / Q000276:immunology*; D018353:Rhabdoviridae Infections / Q000276:immunology / Q000821:virology; D018116:Vesiculovirus / Q000276:immunology / Q000502:physiology; D014779:Virus Replication
chemical_list: D053492:Elafin; D050838:Interferon Regulatory Factor-3; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; C506806:PI3 protein, human; D012367:RNA, Viral