Selective alteration of the turnover of interferon beta mRNA in peritoneal macrophages from LPS-hyporesponsive mice and its role in the defective expression of spontaneous interferon.
Basal levels of interferon (IFN)-beta mRNA transcription were detected in both freshly explanted LPS-responsive (Lpsn) and LPS-hyporesponsive (Lpsd) peritoneal macrophages (PM). In vitro cultivation of PM resulted in a time-dependent reduction in the level of IFN-beta mRNA, which was far more rapid in Lpsd than in Lpsn PM. Treatment of Lpsn PM with cycloheximide (CHX) resulted in a marked accumulation of IFN-beta mRNA, which was not associated with an increase in IFN-beta gene transcription. However, treatment of Lpsd PM with CHX did not induce accumulation of IFN-beta mRNA. CHX induced the accumulation of IFN-alpha-4 mRNA in both Lpsn and Lpsd PM, CHX enhanced the accumulation of two cytoplasmic factors interacting with AU-rich sequences within the 3' untranslated region of IFN-beta mRNA. We conclude that Lpsd PM exhibit an impaired capacity to stabilize IFN-beta mRNA that may account for their low expression of IFN-beta.
Gessani
S
S
Department of Virology, Istituto Superiore di Sanità, Rome, Italy.
Dieffenbach
C W
CW
Conti
L
L
DiMarzio
P
P
Wilson
K L
KL
Belardelli
F
F
D000818:Animals; D001483:Base Sequence; D003513:Cycloheximide / Q000494:pharmacology; D066298:In Vitro Techniques; D016899:Interferon-beta / Q000187:drug effects / Q000378:metabolism*; D008070:Lipopolysaccharides; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D010529:Peritoneal Cavity / Q000166:cytology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism*; D014158:Transcription, Genetic
D008070:Lipopolysaccharides; D012333:RNA, Messenger; D016899:Interferon-beta; D003513:Cycloheximide