Differential regulation of membrane bound and soluble ICAM 1 in human endothelium and blood mononuclear cells: effects of interferon beta-1a.
The membrane-associated Intercellular Adhesion Molecule 1 (mICAM 1) is fundamental for adhesion of leukocytes to endothelial cells. A soluble form of ICAM 1 (sICAM 1) exists in the human serum, and is seen as marker of disease activity in patients suffering from Multiple Sclerosis (MS). High levels of sICAM 1 have been detected in MS patients benefiting from interferon beta (IFNbeta) treatment, but little is known on the molecular origins of sICAM 1. This study investigated the interrelationship and the mechanisms of production of sICAM 1 and mICAM 1 in human endothelium (Human Umbilical Vein Endothelial Cells, HUVECs) and mononuclear leukocytes (MNL) upon stimulation with IFNbeta-1a and other inducers. We found that the expression of mICAM 1 and the release of sICAM 1 are differentially regulated in both these cytotypes. HUVECs and MNL express specific mRNA for both mICAM 1 and sICAM 1, and modification of the content of each of these transcripts results in regulation of both the ICAM 1 isoforms. We show that IFNbeta-1a is strong regulator of the ICAM 1 RNA splicing machinery. Effect of IFNbeta-1a over expression of the ICAM 1 isoforms might have a relevant immunomoregulatory role in Multiple Sclerosis.
Giorelli
Maurizio
M
Department of Neurologic and Psychiatric Sciences, University of Bari, Bari, Italy. mgiorelli@libero.it
De Blasi
Antonio
A
Defazio
Giovanni
G
Avolio
Carlo
C
Iacovelli
Luisa
L
Livrea
Paolo
P
Trojano
Maria
M
D017398:Alternative Splicing / Q000187:drug effects / Q000235:genetics; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002450:Cell Communication / Q000187:drug effects / Q000235:genetics; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000378:metabolism* / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D020033:Protein Isoforms / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D012995:Solubility / Q000187:drug effects
D020033:Protein Isoforms; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D016899:Interferon-beta; D000068556:Interferon beta-1a