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

Abstract

Human ICAM-expression is up-regulated by IFN-r and TNF-a and synergistically increased by a combination of both. Transient expression of ICAM-l/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-o-dependent complexes that bound to the NF-rcB like sequence at -187 as p65/p50 and p65/c-Rel. The interferon responsive region at -75 was bound by a Statla (p91) containing complex that was activated by both IFN-y and IFN-a. Although both regions were required for synergism, no additional or enhanced binding complexes were observed.

Interferon γ-dependent Induction of Human Intercellular Adhesion Molecule-1 Gene Expression Involves Activation of a Distinct STAT Protein Complex

“…We have observed that both GAS and ISRE do not compete with pI␥RE even at a 1000-fold excess in our experiments using HK cell lysates. Our results are in agreement with the report that shows GBP⅐GAS does not compete with the ICAM-1 IFN␥RE in airway epithelial cells (20) and are in contrast to those obtained by others in MeL JuSo cells (42).…”

IFN-γ or IFN-α Ameliorates Chronic Proliferative Dermatitis by Inducing Expression of Linear Ubiquitin Chain Assembly Complex

“…It has been shown that priming with IFN-g augments NF-kB activation and the expression of NF-kB target genes induced by ligands of TLRs, including LPS in macrophages (47). The molecular mechanism underlying the augmentation of NF-kB activation by IFN-g pretreatment is not well understood, although the combined presence of the binding sites of STAT1, which is an IFN-g-inducible transcriptional activator, and the NF-kB binding sites in the promoter region of many NF-kB target genes has been demonstrated (47)(48)(49). We also showed that IFN-g increases the amount of LUBAC and LPSmediated NF-kB activation in BMDMs.…”

Retroinfusion of NFκB decoy oligonucleotide extends cardioprotection achieved by CD18 inhibition in a preclinical study of myocardial ischemia and retroinfusion in pigs

“…36 Subconfluent cells were transfected with Effectene (Qiagen) containing a construct of firefly luciferase ligated to an NF B-sensitive promotor of the human ICAM-1 gene (277-ICAM-1) 37 and a control construct of renilla luciferase ligated to an NF B-insensitive tyrosin-kinase promotor, 24 h later, cells were stimulated with TNF␣ (100 ng/ml). NF B decoy ODN (2 g/well) containing liposomes were added either at stimulation (0 h) or 24 h before (-24 h).…”