Retinoic acid inhibits basal and interferon-gamma-induced expression of intercellular adhesion molecule 1 in monocytic cells.
Retinoic acid (RA) and 1,25-(OH)2-vitamin D3 (1,25-D3) induced U937 cell maturation into distinct monocytic phenotypes, as demonstrated by up-regulation of CD23 by RA and CD14 by 1,25-D3. Differentiation by RA but not by 1,25-D3 was associated with reduction of basal and complete suppression of interferon-gamma (IFN-gamma)-stimulated intercellular adhesion molecule 1 (ICAM-1) expression. Induction of cyclooxygenase activity by RA and attenuation of basal ICAM-1 expression exhibited similar kinetics. Treatment with indomethacin prevented and prostaglandin E2 (PGE2), dibutyryl-cAMP, or forskolin mimicked reduction of basal ICAM-1 expression by RA, indicating that this effect of RA is mediated by PGE2 synthesis and subsequent cAMP elevation. In contrast, suppression of IFN-gamma-induced ICAM-1 expression by RA was only partly reversible by indomethacin, suggesting that inhibition of IFN-gamma stimulation was not completely due to cyclooxygenase induction. RA did not always counter-act IFN-gamma, as it cooperated with IFN-gamma in down-regulating very late activation antigen 4. Specific polymerase chain reaction and Northern blotting of ICAM-1 mRNA revealed that RA suppressed ICAM-1 induction by IFN-gamma at the transcriptional level. RA also blocked ICAM-1 induction by IFN-gamma in isolated human blood monocytes. In conclusion, inhibition of basal and stimulated ICAM-1 expression in monocytic cells may provide a mechanism for beneficial anti-inflammatory effects of retinoids.
Weber
C
C
Institut für Prophylaxe der Kreislaufkrankheiten, University of Munich, Germany.
Calzada-Wack
J C
JC
Goretzki
M
M
Pietsch
A
A
Johnson
J P
JP
Ziegler-Heitbrock
H W
HW
D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D003994:Bucladesine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002117:Calcitriol / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis / Q000494:pharmacology; D004790:Enzyme Induction; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology*; D018950:Lipopolysaccharide Receptors; D009000:Monocytes / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017455:Receptors, IgE / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018950:Lipopolysaccharide Receptors; D012333:RNA, Messenger; D017455:Receptors, IgE; D018799:Intercellular Adhesion Molecule-1; D005576:Colforsin; D000001:Calcimycin; D014212:Tretinoin; D003994:Bucladesine; D007371:Interferon-gamma; D011451:Prostaglandin-Endoperoxide Synthases; D002117:Calcitriol; D015232:Dinoprostone; D007213:Indomethacin