CD14-dependent modulation of NF-κB alternative splicing in the lung after burn injury

Ho H Phan, Kiho Cho, Kelly S. Sainz-Lyon, Soowan Shin, David G Greenhalgh

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Nuclear factor kappa-B (NF-κB), a key downstream player of the LPS signaling pathway, has been shown to undergo alternative splicing in in vitro studies. In this study, we examined the effect of injury and the role of CD14 on NF-κB alternative splicing using a murine burn model. CD14 knockout and respective wild-type mice were sacrificed after 18% total body surface area burn. RT-PCR and subsequent sequencing analysis revealed that injury induced multiple novel splicing variants of relA, relB, and NF-κB2 in the lungs of CD14 knockout but not wild-type mice. These novel variants resulted either from exon skipping, alternative usage of splicing signals, or intron retention. All but one variant resulted in a frameshift leading to premature termination of translation. These splicing variants encoded for proteins that lacked the domains essential for NF-κB transcription factor functions. Two NF-κB2 variants acquired only minor changes in their C-terminus that might affect their post-translational cleavage into active isoforms. These results suggest that alternative splicing may be one of the mechanisms by which NF-κB activity in the lungs can be regulated after injury. Furthermore, the CD14-mediated LPS signaling pathway may play a role in the regulation of NF-κB alternative splicing in the lungs after injury.

Original languageEnglish (US)
Pages (from-to)121-129
Number of pages9
JournalGene
Volume371
Issue number1
DOIs
StatePublished - Apr 12 2006

Keywords

  • LPS
  • p100
  • RelA
  • RelB
  • Transcript
  • Variant

ASJC Scopus subject areas

  • Genetics

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