Premium
Efficient inhibition of macrophage TNF‐α production upon targeted delivery of K48R ubiquitin
Author(s) -
ANTONELLI ANTONELLA,
CRINELLI RITA,
BIANCHI MARZIA,
CERASI AURORA,
GENTILINI LUCIA,
SERAFINI GIORDANO,
MAGNANI MAURO
Publication year - 1999
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1999.01202.x
Subject(s) - ubiquitin , lipopolysaccharide , tumor necrosis factor alpha , macrophage , chemistry , microbiology and biotechnology , intracellular , transfection , stimulation , recombinant dna , biology , biochemistry , in vitro , immunology , gene , endocrinology
K48R ubiquitin (K48R‐Ub) is an analogue of native ubiquitin that does not form polyubiquitin chain conjugates. Targeted delivery of this recombinant mutant ubiquitin to human macrophages results in an intracellular increase in the ubiquitin analogue. IkBα polyubiquitination and degradation were significantly inhibited in K48R‐Ub targeted macrophages upon stimulation with lipopolysaccharide. The ability to reduce IkBα degradation was also associated with a reduced production of TNF‐α, the gene of which is under NF‐kB control. At a concentration of 0.1 μ M , dexamethasone was less effective than K48R‐Ub in preventing IkBα depletion and TNF‐α release. These data suggest that ubiquitin analogues are potent suppressors of TNF‐α release in macrophages.