Interleukins and interferons: yin-yang modulators of PGH synthase in human macrophages.
Prostaglandin H synthase (PGHs) not only is an unstable enzyme, mainly when it is challenged with substrate, but its mRNA is one of the shortest lived species so far identified in mammalian cells. Therefore, signals regulating its level are critical for the role it plays in many cells. The expression of genes coding for PGHs appears to be under the control of polypeptide growth factors. This is in accordance with our previous data showing that a colony stimulating factor-1 (CSF-1)-like factor induces the de novo synthesis of PGHs in human monocytes, as demonstrated by immunoblotting. Here we extend this concept by showing that interleukin (IL)-1 alpha behaves as a potent inducer of PGHs in human macrophages, as indicated by the block in its action due to the addition of RNA and protein synthesis inhibitors. Interferons (IFNs) alpha and beta, however, inhibit prostanoid production in a dose-dependent fashion mainly when macrophages activated by serum are tested. Thus, the PGHs system appears to be under a fine control, CSF-1 being the main regulator during the differentiation from pro-monocyte to monocyte and from monocyte to macrophage, and IL-1 (and perhaps IL-2) as well as IFN alpha and beta, the regulators during differentiation and/or proliferation of human macrophages.
Bartolini
G
G
Department of Experimental Biology, University of Bologna, Italy.
Orlandi
M
M
Chiricolo
M
M
Licastro
F
F
Zambonelli
P
P
Minghetti
L
L
Tomasi
V
V
D003513:Cycloheximide / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis / Q000378:metabolism; D006801:Humans; D007372:Interferons / Q000502:physiology*; D007375:Interleukin-1 / Q000037:antagonists & inhibitors; D007378:Interleukins / Q000502:physiology*; D008264:Macrophages / Q000201:enzymology*; D009000:Monocytes / Q000201:enzymology; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D013929:Thromboxane B2 / Q000096:biosynthesis / Q000378:metabolism
D007375:Interleukin-1; D007378:Interleukins; D013929:Thromboxane B2; D007372:Interferons; D003513:Cycloheximide; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone