Induced expression of the new cytokine, activin A, in human monocytes: inhibition by glucocorticoids and retinoic acid.
The capacity of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF), glucocorticoids or all-trans-retinoic acid to modulate production of activin A by human monocytes was studied. It was shown that GM-CSF stimulated monocytes to accumulate activin A RNA after as few as 4 hr of incubation, reaching a peak of stimulation at approximately 16 hr of incubation. The activin A transcripts accumulated in the monocytes after stimulation with only 5 U/ml of GM-CSF and reached a maximum plateau level of expression between 25 and 50 U/ml of GM-CSF. Biologically active activin A molecules were detected in the conditioned media by a bioassay, performed both in the absence and presence of a neutralizing antiserum for activin A. Accumulation of bioactive activin A in conditioned medium of monocyte cultures was detected after 24 hr of incubation with GM-CSF and high levels of activin A were maintained for 72 hr. The production of the dimeric beta A beta A in these monocytes was further confirmed by sandwich enzyme-linked immunosorbent assay (ELISA) specific for activin A. In contrast to the stimulatory effect of GM-CSF, hydrocortisone, dexamethasone or all-trans-retinoic acid at 1 x 10(-7) to 1 x 10(-5) M inhibited the constitutive expression of activin A and greatly suppressed the GM-CSF-stimulated production. Thus, the expression of activin A is modulated in monocytes by different agents. These observations may imply new roles for activin A at sites of inflammation where monocytes accumulate.
Yu
J
J
Department of Molecular & Experimental Medicine, Scripps Research Institute, La Jolla, CA 92037, USA.
Shao
L E
LE
Frigon
N L
NL
Lofgren
J
J
Schwall
R
R
D028341:Activins; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015152:Blotting, Northern; D018929:Cell Culture Techniques; D017077:Culture Media, Conditioned; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives* / Q000494:pharmacology; D007265:Inhibins / Q000096:biosynthesis*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D014212:Tretinoin / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D017077:Culture Media, Conditioned; D011994:Recombinant Proteins; D028341:Activins; D014212:Tretinoin; D007265:Inhibins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C007133:hydrocortisone hemisuccinate; D006854:Hydrocortisone