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Cytokine‐inducible expression in endothelial cells of an I kappa B alpha‐like gene is regulated by NF kappa B.
Author(s) -
Martin R.,
Vanhove B.,
Cheng Q.,
Hofer E.,
Csizmadia V.,
Winkler H.,
Bach F.H.
Publication year - 1993
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/j.1460-2075.1993.tb05938.x
Subject(s) - biology , nfkb1 , kappa , cytokine , gene expression , alpha (finance) , gene , microbiology and biotechnology , regulation of gene expression , genetics , transcription factor , medicine , linguistics , philosophy , construct validity , nursing , patient satisfaction
The transient expression of many different genes is mediated by the inducible transcription factor p50‐p65 NF kappa B, which in turn is regulated by complex formation with its inhibitor I kappa B alpha. We describe here that in porcine aortic endothelial cells, either IL‐1 alpha, TNF alpha or LPS upregulates an inhibitor of NF kappa B which we refer to as ECI‐6. ECI‐6 is by structural and functional criteria an I kappa B alpha protein, the porcine homologue of MAD‐3, pp40 and RL/IF‐1. We have studied the promoter of the ECI‐6/I kappa B alpha gene and provide three lines of evidence that its expression is directly regulated by NF kappa B. First, the 5′ regulatory region of ECI‐6/I kappa B alpha contains two sites that bind NF kappa B in electrophoretic mobility shift assays. Second, expression following transfection of an ECI‐6/I kappa B alpha promoter‐luciferase reporter construct is dependent on a co‐transfected NF kappa B‐p65 subunit. Third, pretreatment of endothelial cells with antioxidants, agents that inhibit activation of NF kappa B, inhibit the expression of ECI‐6/I kappa B alpha. We conclude that the regulated expression of ECI‐6/I kappa B alpha could represent a novel feedback mechanism by which NF kappa B downregulates its own activity after transient activation of target genes has been achieved.