Cross-linking of intercellular adhesion molecule 1 (CD54) induces AP-1 activation and IL-1beta transcription.
Leukocytes adhere to target cells through their integrins and play a crucial role in self-defense, inflammation, and differentiation. Intercellular adhesion molecule-1 (ICAM-1; CD54) is a representative ligand for integrins and is expressed on many cell types, some of which are targets for leukocyte adhesion. Recent studies suggest that adhesion molecules function not only as a cellular glue, but also as a signal transducer. However, it remains to be clearly defined whether engagement of ICAM-1 is able to induce activation signals in target cells. In rheumatoid synovium, synovial cells are known to express abundant ICAM-1 and produce multiple inflammatory cytokines, such as IL-1beta. In this study, we provide the first evidence that ICAM-1 engagement induces activation of the transcription factor AP-1 and transcription of the IL-1beta gene using a specific Ab to cross-link ICAM-1 on a rheumatoid synovial cell line (E11 cells). This evidence includes ICAM-1 cross-linking-dependent induction of 1) in situ IL-1beta transcription and protein synthesis, 2) transiently transfected chloramphenicol acetyltransferase (CAT) reporter plasmids containing both the IL-1beta LPS-responsive enhancer (between -3134 and -2729) as well as multiple copies of an AP-1 site from this enhancer (between -3117 and -3111), and 3) the binding of a Jun/Fos family complex to this AP-1 site. Thus, ICAM-1 not only functions as a glue for integrin binding, but also as a transducer for AP-1 activation signals important for IL-1beta gene transcription.
Koyama
Y
Y
The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
Tanaka
Y
Y
Saito
K
K
Abe
M
M
Nakatsuka
K
K
Morimoto
I
I
Auron
P E
PE
Eto
S
S
D000818:Animals; D000911:Antibodies, Monoclonal; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D003432:Cross-Linking Reagents; D004247:DNA / Q000235:genetics / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D004742:Enhancer Elements, Genetic / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000737:chemistry / Q000378:metabolism*; D007375:Interleukin-1 / Q000235:genetics*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D010957:Plasmids / Q000235:genetics; D017452:Receptors, IgG / Q000378:metabolism; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection
D000911:Antibodies, Monoclonal; D003432:Cross-Linking Reagents; D017931:DNA Primers; D007375:Interleukin-1; D008070:Lipopolysaccharides; D017452:Receptors, IgG; D018808:Transcription Factor AP-1; D018799:Intercellular Adhesion Molecule-1; D004247:DNA; D015500:Chloramphenicol O-Acetyltransferase