These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: A distinct element involved in lipopolysaccharide activation of the tumor necrosis factor-alpha promoter in monocytes.
    Author: Diaz B, Lopez-Berestein G.
    Journal: J Interferon Cytokine Res; 2000 Aug; 20(8):741-8. PubMed ID: 10954918.
    Abstract:
    To delineate the functional role of the tumor necrosis factor-alpha (TNF-alpha) activator protein-1 (AP-1)/cAMP-responsive element (CRE)-like binding element (TAC), we transfected the TNF-alpha promoter lacking TAC into THP-1 monocytic cells and stimulated with lipopolysaccharide (LPS). Chloramphenicol acetyltransferase (CAT) activity was reduced by 22-fold, suggesting that TAC plays a role in LPS induction of the TNF-alpha promoter. Exposure to LPS resulted in the maximum release of soluble TNF-alpha by 2 h. Electrophoretic mobility shift assays (EMSA) using the TAC element as a probe showed a unique pattern for LPS-activated cells: the disappearance of the upper band of a doublet seen in untreated and all-trans retinoic acid (ATRA)-treated cells. Supershift analysis identified c-Jun and activating transcription factor-2 (ATF-2) as components of the LPS-stimulated binding complex. Jun N-terminal kinase (JNK), a known phosphorylator of c-Jun and ATF-2, increased in activity in LPS-stimulated monocytes. ATRA, on the contrary, did not activate JNK activity up to 72 h. Nuclear extracts from LPS-stimulated cells showed an increase in phosphorylated c-Jun by immunoblotting. Likewise, phosphorylated c-Jun bound to the TAC element, suggesting that c-Jun is activated by JNK to transactivate the TNF-alpha promoter in LPS-treated monocytes. Thus, phosphorylated c-Jun and ATF-2 play a role in activating the TAC element of the TNF-alpha promoter.
    [Abstract] [Full Text] [Related] [New Search]