Regulation of bacteria-induced intercellular adhesion molecule-1 by CCAAT/enhancer binding proteins

Lori J. Manzel, Cecilia L. Chin, Mark A. Behlke, Dwight C. Look

Research output: Contribution to journalArticle

10 Scopus citations


Direct interaction between bacteria and epithelial cells may initiate or amplify the airway response through induction of epithelial defense gene expression by nuclear factor--κB (NF--κB). However, multiple signaling pathways modify NF--κB effects to modulate gene expression. In this study, the effects of CCAAT/enhancer binding protein (C/EBP) family members on induction of the leukocyte adhesion glycoprotein intercellular adhesion molecule-1 (ICAM-1) was examined in primary cultures of human tracheobronchial epithelial cells incubated with nontypeable Haemophilus influenzae. Increased ICAM-1 gene transcription in response to H. influenzae required gene sequences located at -200 to -135 in the 5'-flanking region that contain a C/EBP-binding sequence immediately upstream of the NF--κB enhancer site. Constitutive C/EBPβ was found to have an important role in epithelial cell ICAM-1 regulation, while the adjacent NF-kB sequence binds the RelA/p65 and NF--κB1/p50 members of the NF-KB family to induce ICAM-1 expression in response to H. influenzae. The expression of C/EBP proteins is not regulated by p38 mitogen-activated protein kinase activation, but p38 affects gene transcription by increasing the binding of TATA- binding protein to TATA-box-containing gene sequences. Epithelial cell ICAM-1 expression in response to H. influenzae was decreased by expressing dominant-negative protein or RNA interference against C/EBPb, confirming its role in ICAM-1 regulation. Although airway epithelial cells express multiple constitutive and inducible C/EBP family members that bind C/EBP sequences, the results indicate that C/EBPb plays a central role in modulation of NF--κB-dependent defense gene expression in human airway epithelial cells after exposure to H. influenzae.

Original languageEnglish
Pages (from-to)200-210
Number of pages11
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Issue number2
StatePublished - Feb 1 2009
Externally publishedYes


  • Inflammation
  • Mitogen-acti-vated protein kinase
  • NF-κB
  • Transcription factors

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