| Literature DB >> 9014821 |
S Y Jeong1, J H Lee, H S Kim, S H Hong, C H Cheong, I K Kim.
Abstract
The effects of 3-deazaadenosine (DZA), 3-deaza(+/-)-aristeromycin (DZAri) and 3-deazaneplanocin (DZNep) on tumour necrosis factor-alpha (TNF-alpha) production were examined in the mouse macrophage cell line, RAW264.7, stimulated with lipopolysaccharide (LPS). The 3-deazaadenosine analogues inhibited the TNF-alpha production and the inhibition was dependent upon the concentration of the analogue. DZA reduced the level of TNF-alpha mRNA suggesting that DZA acts at a transcriptional step. In contrast, DZAri and DZNep had little effect on mRNA levels for TNF-alpha, implying that these compounds inhibit a post-transcriptional or translational biosynthetic step of TNF-alpha synthesis. The observation that homocysteine (Hcy) potentiated the DZA inhibition of TNF-alpha production and of TNF-alpha mRNA levels suggests that the inhibition of TNF-alpha production may be caused by elevated levels of 3-deazaadenosylhomocysteine (DZAHcy). The results show that the 3-deazaadenosine analogues are potent inhibitors of TNF-alpha production in the RAW264.7 cell line stimulated with LPS and suggest that these analogues may be effective agents for the treatment of diseases in which TNF-alpha plays an important pathogenic role.Entities:
Mesh：
Substances：
Year: 1996 PMID： 9014821 PMCID： PMC1456586 DOI： 10.1046/j.1365-2567.1996.d01-781.x
Source DB: PubMed Journal: Immunology ISSN： 0019-2805 Impact factor: 7.397