Recombinant human C5a induces transcription but not translation of interleukin-1 beta mRNA in human monocytes.
The effect of recombinant human C5a (rhC5a) on the synthesis of interleukin-1 beta (IL 1 beta) was investigated in highly purified human monocytes, isolated by leukapheresis and counter-current elutriation. RhC5a induced IL 1 beta mRNA synthesis in a dose- and time-dependent manner; maximal induction was achieved at 3 h with rhC5a concentrations of 200 to 500 ng/ml. The IL 1 beta mRNA induction with rhC5a was about 75% of the response observed using lipopolysaccharide (LPS) as the stimulus (300 ng/ml). On the other hand, rhC5a in optimal concentrations only weakly stimulated IL 1 beta protein synthesis, as measured by a two-site-directed enzyme-linked immunoassay. When LPS- or C5a-stimulated RNA was used to program IL 1 beta synthesis in an in vitro translation system from rabbit reticulocytes, no difference in translational efficiency was observed. Our results indicate that, in human monocytes, two signals for IL 1 beta gene expression are necessary, one signal for transcriptional activation and a second signal to induce translation of the mRNA.
Geiger
T
T
Ciba-Geigy Ltd., Research Department, Basel, Switzerland.
Rordorf
C
C
Galakatos
N
N
Seligmann
B
B
Henn
R
R
Lazdins
J
J
Vosbeck
K
K
D015936:Complement C5a / Q000276:immunology*; D005786:Gene Expression Regulation; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics*; D008070:Lipopolysaccharides / Q000276:immunology; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins / Q000276:immunology; D014158:Transcription, Genetic
D007375:Interleukin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D011994:Recombinant Proteins; D015936:Complement C5a