KLF6 and iNOS regulates apoptosis during respiratory syncytial virus infection

Cell Immunol. 2013 May-Jun;283(1-2):1-7. doi: 10.1016/j.cellimm.2013.06.002. Epub 2013 Jun 18.

Abstract

Human respiratory syncytial virus (RSV) is a highly pathogenic lung-tropic virus that causes severe respiratory diseases. Enzymatic activity of inducible nitric oxide (iNOS) is required for NO generation. Although NO contributes to exaggerated lung disease during RSV infection, the role of NO in apoptosis during infection is not known. In addition, host trans-activator(s) required for iNOS gene expression during RSV infection is unknown. In the current study we have uncovered the mechanism of iNOS gene induction by identifying kruppel-like factor 6 (KLF6) as a critical transcription factor required for iNOS gene expression during RSV infection. Furthermore, we have also uncovered the role of iNOS as a critical host factor regulating apoptosis during RSV infection.

Keywords: Apoptosis; BMDMs; ChIP; Inducible nitric oxide synthase; KLF6; KO; Kruppel-like factor 6; L-NIL; N(6)-(1-iminoethyl)-l-lysine dihydrochloride; NO; Nitric oxide; RSV; Respiratory syncytial virus; Transcription factor; WT; bone marrow-derived macrophages; chromatin immuno-precipitation; iNOS; inducible nitric oxide synthase; knock-out; kruppel-like factor 6; nitric oxide; respiratory syncytial virus; wild type.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Chromatin Immunoprecipitation
  • Humans
  • Kruppel-Like Factor 6
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism*
  • Mice
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Respiratory Syncytial Virus Infections / genetics
  • Respiratory Syncytial Virus Infections / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcriptional Activation

Substances

  • KLF6 protein, human
  • Kruppel-Like Factor 6
  • Kruppel-Like Transcription Factors
  • Proto-Oncogene Proteins
  • NOS2 protein, human
  • Nitric Oxide Synthase Type II