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Updated: Aug 9, 2026

Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
Interferon gamma-dependent induction of human intercellular adhesion molecule-1 gene expression involves activation
S M Naik1, N Shibagaki, L J Li
1Department of Dermatology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Abstract:
In response to interferon gamma (IFNgamma), intercellular adhesion molecule-1 (ICAM-1) is expressed on human keratinocytes, a cell type that is critically involved in cutaneous inflammation. An ICAM-1 5' regulatory region palindromic response element, pIgammaRE, has been shown to confer IFNgamma-dependent transcription enhancement. By electrophoretic mobility shift assays (EMSA), pIgammaRE forms a distinct complex with proteins from IFNgamma-treated human keratinocytes, termed gamma response factor (GRF). Binding of GRF is tyrosine phosphorylation-dependent, and mutations of pIgammaRE that disrupt the palindromic sequence or alter its spatial relationship abrogate GRF binding. Supershift EMSAs using antibodies to characterized STAT proteins suggest that GRF contains a Stat1alpha-like protein; however, non-ICAM-1 IFNgamma-responsive elements (REs) known to bind Stat1alpha homodimers fail to compete for GRF binding in EMSA, and pIgammaRE does not cross-compete with these REs that complex with homodimeric stat1alpha. The pIgammaRE x GRF complex also displays a distinctly different electrophoretic mobility compared to that of IFNgammaREs complexed to homodimeric Stat1alpha. These findings indicate that a distinct complex containing a Stat1alpha-like protein mediates IFNgamma-induced ICAM-1 gene transcription and identifies a subset of IFNgamma-responsive genes that appear to be regulated by this complex.
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