The role of NF-kappa B and NF-IL6 transactivating factors in the synergistic activation of human serum amyloid A gene expression by interleukin-1 and interleukin-6.
J Biol Chem
; 268(34): 25624-31, 1993 Dec 05.
Article
in En
| MEDLINE
| ID: mdl-8244997
ABSTRACT
To understand the mechanisms by which large increases in serum amyloid A (SAA) occur during the acute phase response, human hepatoma cells were transfected with SAA2 gene reporter plasmids and stimulated with combinations of cytokines. Although interleukin-1 (IL-1) and interleukin-6 (IL-6) stimulated transcription from this promoter individually, addition of both mediators produced a response between two and nine times greater than the expected additive response. This synergistic activation was dependent on the integrity of at least two cis-acting sequences in the SAA2 enhancer. The SAA2 NF-kappa B site was required functionally for the response to both IL-1 and IL-6 alone as well as for synergistic activation; however, IL-6 did not directly induce binding of nuclear proteins to the NF-kappa B sequence. A NF-IL6 site was required for full induction by IL-1 and IL-6, and also mediated strong transactivation by recombinant NF-IL6. Furthermore, transfected NF-IL6 synergized strongly with co-transfected NF-kappa B, particularly with RelA (p65). However synergy between IL-1 and IL-6 was only partly reduced by mutation of the NF-IL6 site, indicating further levels of interaction in addition to the NF-kappa B/NF-IL6 cooperativity.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Transcription Factors
/
Serum Amyloid A Protein
/
Nuclear Proteins
/
Gene Expression
/
NF-kappa B
/
Interleukin-6
/
Interleukin-1
/
DNA-Binding Proteins
Limits:
Humans
Language:
En
Journal:
J Biol Chem
Year:
1993
Document type:
Article
Affiliation country:
Reino Unido