title: Krüppel-like factor 6 regulates transforming growth factor-β gene expression during human respiratory syncytial virus infection.
abstract: BACKGROUND
  Human respiratory syncytial virus (RSV) infection is associated with airway remodeling and subsequent asthma development. Transforming growth factor-beta (TGF) plays a crucial role in asthma development. The mechanism regulating TGF gene expression during RSV infection is not known. Kruppel-like factor family of transcription factors are critical regulators of cellular/tissue homeostasis. Previous studies have shown that Kruppel-like factor 6 (KLF6) could function as a trans-activator of TGF gene; however, whether KLF members play a role during infection is unknown. In the current study we have evaluated the role of KLF6 during TGF expression in RSV infected cells.
  
  
  RESULTS
  Silencing KLF6 expression by shRNA led to drastic inhibition in TGF production during RSV infection, as assessed by ELISA analysis of medium supernatants. RT-PCR analysis revealed loss of TGF expression in KLF6 silenced cells. Chromatin-immunoprecipitation assay conducted with RSV infected cells showed binding of KLF6 protein to the TGF promoter during RSV infection. We further observed reduced RSV infectivity in KLF6 silenced cells and in cells incubated with TGF neutralizing antibody. In contrast, enhanced RSV infection was noted in cells incubated with purified TGF.
  
  
  CONCLUSIONS
  We have identified KLF6 as a key transcription factor required for trans-activation of TGF gene during RSV infection. Moreover, TGF production is required for efficient RSV infection and thus, KLF6 is also required for efficient RSV infection by virtue of KLF6 dependent TGF production during infection.
authors.affiliation: Department of Microbiology and Immunology, The University of Texas Health Science Center at San Antonio, USA.
authors.forename: Victoria
authors.initials: V
authors.lastname: Mgbemena
authors.forename: Jesus
authors.initials: J
authors.lastname: Segovia
authors.forename: TeHung
authors.initials: T
authors.lastname: Chang
authors.forename: Santanu
authors.initials: S
authors.lastname: Bose
mesh_terms: D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000378:metabolism / Q000821:virology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D020868:Gene Silencing; D054884:Host-Pathogen Interactions; D006801:Humans; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D018113:Respiratory Syncytial Virus, Human / Q000472:pathogenicity*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
chemical_list: C105465:KLF6 protein, human; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors; D011518:Proto-Oncogene Proteins; D016212:Transforming Growth Factor beta