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Control of HILDA/LIF Gene Expression in Activated Human Monocytes a
Author(s) -
GROLLEAU DOMINIQUE,
SOULILLOU JEANPAUL,
ANEGON IGNACIO
Publication year - 1991
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1991.tb17219.x
Subject(s) - citation , humanities , library science , art , computer science
In the present study we have investigated some of the mechanisms involved in HILDA/LIF gene expression in activated human monocytes and compared them to those of G-CSF gene expression, another monocyte-derived cytokine. In the absence of added stimuli, HILDA/LIF mRNA was barely detectable in monocytes. HILDA/LIF mRNA accumulation was weakly induced by stimuli such as LPS or phorbol ester alone, and in a synergistic manner when they were used in combination with 1,25-dihydroxyvitamin D3. Nuclear run-on transcription analysis in U937 cells did not detect an increase of HILDA/LIF gene transcription upon phorbol ester and 1,25-dihydroxyvitamin D3 stimulation. Posttranscriptional control of HILDLA/LIF mRNA levels by an increase in mRNA half-life was demonstrated in the synergy between phorbol ester and 1,25-dihydroxyvitamin D3 and in the superinduction of HILDA/LIF transcript accumulation when CHX was added to stimulated cells shortly before cell harvesting. HILDA/LIF mRNA expression was largely inhibited when U937 cells were treated with CHX either at the onset or 4 h after the beginning of the stimulation period. When CHX was added 2 h before cell harvesting, a superinduction of mRNA accumulation was obtained. G-CSF mRNA accumulation showed a different pattern of response to the same stimuli, in particular a higher rate of response to LPS. In contrast to HILDA/LIF, an augmentation of G-CSF gene transcription was detected in activated monocytic cells when compared to controls. These studies indicate that HILDA/LIF gene expression by phorbol ester- and 1,25-dihydroxyvitamin D3-treated human monocytes has a relatively specific regulation, as compared to G-CSF gene expression, and that it is largely dependent on posttranscriptional mechanisms probably acting through labile, newly synthesized proteins.