Inhibitory effect of recombinant intracellular interleukin 1 receptor antagonist on endothelial cell activation.
This investigation was designed to elucidate whether an intracellular version of interleukin 1 receptor antagonist (icIL-1ra) interferes with the action of IL-1 at the level of vascular cells. Recombinant icIL-1ra inhibited the IL-1-induced production of IL-6, IL-8 and monocyte chemotactic protein by human endothelial cells (HEC). Moreover, icIL-1ra inhibited induction of adhesion molecules by IL-1. Endotoxin lipopolysaccharide (LPS), an IL-1 inducer, stimulated a spectrum of functions in EC similar to that activated by IL-1, but icIL-1ra did not interfere with the LPS activation of EC. This observation suggests that induction of extracellular IL-1 is not an important intermediate event in the response of EC to LPS. Unlike LPS-stimulated monocytes, EC exposed to different inducers did not express appreciable levels of IL-1ra mRNA transcripts as assessed by northern blot analysis. IL-1ra produced by mononuclear phagocytes, represents a negative regulator circuit of the action of IL-1 on EC and could be important in the control of vascular participation in inflammation and immunity.
Bertini
R
R
Instituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Sironi
M
M
Martin-Padura
I
I
Colotta
F
F
Rambaldi
S
S
Bernasconi
S
S
Ghezzi
P
P
Haskill
S J
SJ
Liu
D
D
Mantovani
A
A
D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002478:Cells, Cultured; D018932:Chemokine CCL2; D002630:Chemotactic Factors / Q000096:biosynthesis; D003864:Depression, Chemical; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000187:drug effects*; D004731:Endotoxins / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007231:Infant, Newborn; D018799:Intercellular Adhesion Molecule-1; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007378:Interleukins / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors*; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins; D019010:Vascular Cell Adhesion Molecule-1
D015815:Cell Adhesion Molecules; D018932:Chemokine CCL2; D002630:Chemotactic Factors; D004731:Endotoxins; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D007378:Interleukins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D016178:Granulocyte-Macrophage Colony-Stimulating Factor