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3‐deazaadenosine analogues inhibit the production of tumour necrosis factor‐α in RAW264.7 cells stimulated with lipopolysaccharide
Author(s) -
JEONG S.Y.,
LEE J.H.,
KIM H.S.,
HONG S.H.,
CHEONG C.H.,
KIM I.K.
Publication year - 1996
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.1996.d01-781.x
Subject(s) - tumor necrosis factor alpha , lipopolysaccharide , cell culture , biology , messenger rna , microbiology and biotechnology , biochemistry , immunology , gene , genetics
The effects of 3‐deazaadenosine (DZA), 3‐deaza(±)‐ aristeromycin (DZAri) and 3‐deazaneplanocin (DZNep) on tumour necrosis factor‐α (TNF‐α) production were examined in the mouse macrophage cell line, RAW264.7, stimulated with lipopolysaccharide (LPS). The 3‐deazaadenosine analogues inhibited the TNF‐α production and the inhibition was dependent upon the concentration of the analogue. DZA reduced the level of TNF‐α mRNA suggesting that DZA acts at a transcriptional step. In contrast, DZAri and DZNep had little effect on mRNA levels for TNF‐α, implying that these compounds inhibit a post‐transcriptional or translational biosynthetic step of TNF‐α synthesis. The observation that homocysteine (Hcy) potentiated the DZA inhibition of TNF‐α production and of TNF‐α mRNA levels suggests that the inhibition of TNF‐α production may be caused by elevated levels of 3‐deazaadenosylhomocysteine (DZAHcy). The results show that the 3‐deazaadenosine analogues are potent inhibitors of TNF‐α 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‐α plays an important pathogenic role.