Synergistic activation of intercellular adhesion molecule 1 (ICAM-1) by TNF-α and IFN-γ is mediated by p65/p50 and p65/c-Rel and interferon-responsive factor Statlα (p91) that can be activated by both IFN-γ and IFN-α

• Published in: FEBS letters Vol. 354; no. 2; pp. 220 - 226
• Main Authors: Jahnke, Andreas, P. Johnson, Judith
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 07.11.1994
• Subjects: Cell adhesion molecule; Cytokine; DNA-binding protein; EMSA, electromobility shift assay; GAF, γ-activated factor; GAS, γ-activated sequence; Genetics; ICAM-1, intercellular adhesion molecule-1; IFN, interferon; IRE, interferon-responsive element; ISGF, interferon α-stimulated gene factor; Promoter region; Regulatory-sequence; RRBE, Rel-related protein binding element; TNF, tumor necrosis factor; TNF-R, TNF-α receptor; Trans-activation; IFN, interferon; IRE, interferon-responsive element; TNF, tumor necrosis factor; TNF-R, TNF-α receptor; Cell adhesion molecule; Cytokine; EMSA, electromobility shift assay; GAS, γ-activated sequence; Trans-activation; Promoter region; ICAM-1, intercellular adhesion molecule-1; ISGF, interferon α-stimulated gene factor; DNA-binding protein; Genetics; Regulatory-sequence; GAF, γ-activated factor; RRBE, Rel-related protein binding element
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/0014-5793(94)01130-3

Human ICAM-1 expression is up-regulated by IFN-γ and TNF-α, and synergistically increased by a combination of both. Transient expression of ICAM-1/luciferase constructs led to definition of the regulatory regions mediating the cytokine response and showed that both are necessary for synergism. Immunochemical electromobility shift assays identified the TNF-α-dependent complexes that bound to the NF-κB like sequence at −187 as p65/p50 and p65/c-Rel. The interferon responsive region at −75 was bound by a Statlα (p91) containing complex that was activated by both IFN-γ and IFN-α. Although both regions were required for synergism, no additional or enhanced binding complexes were observed.