The down-regulation of IL-6-stimulated fibrinogen steady state mRNA and protein levels by human recombinant IL-1 is not PGE2-dependent: effects of IL-1 receptor antagonist (IL-1RA).
Infections, trauma and inflammatory processes induce a host response with increases in a large group of structurally and functionally diverse plasma proteins. Parental administration of foreign proteins also induce an increase in plasma fibrinogen. Interleukin-6 (IL-6) is a monocyte-derived mediator and has regulatory effects on acute phase protein genes which result in the induction of fibrinogen synthesis in primary hepatocytes, while the addition of interleukin-1 (IL-1) exerts a negative modulating influence on the IL-6-stimulated fibrinogen. In order to understand the mechanisms by which IL-1 inhibits IL-6-stimulated fibrinogen transcription and translation, and since IL-1 is believed to act through PGE2 stimulation, we have studied the influence of PGE2 in IL-6 or IL-1, alone and in combination, on Fg mRNA expression (by Northern blot analysis) and the influence of PGE2, indomethacin, and arachidonic acid on Fg secretion. Moreover, since human recombinant interleukin-1 receptor antagonist (hrIL-1ra) is a strong inhibitor of IL-1 induced IL-1 transcription and translation and has an inhibitory effect on PGE2, we have studied the effects of IL-1ra on the down-regulation of IL-6 stimulated fibrinogen by IL-1, using an Fg ELISA method.(ABSTRACT TRUNCATED AT 250 WORDS)
Conti
P
P
Immunology Division, University of Chieti Medical School, Italy.
Bartle
L
L
Barbacane
R C
RC
Reale
M
M
Sipe
J D
JD
D016718:Arachidonic Acid / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology*; D015536:Down-Regulation; D005340:Fibrinogen / Q000096:biosynthesis / Q000235:genetics*; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology*; D009288:Naproxen / Q000494:pharmacology; D010741:Phospholipases A / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D000093242:Interleukin-6 Inhibitors
D016718:Arachidonic Acid; D015232:Dinoprostone; D005340:Fibrinogen; D007213:Indomethacin; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D015850:Interleukin-6; D009288:Naproxen; D010741:Phospholipases A; D012333:RNA, Messenger; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D000093242:Interleukin-6 Inhibitors; C507763:IL1RN protein, human