Adult human vascular endothelial cells express the IL6 gene differentially in response to LPS or IL1.
We investigated the regulation of IL6 biological activity, de novo synthesis, and mRNA levels in adult vascular endothelial cells (EC) by bacterial endotoxin or inflammatory cytokines. Cells incubated without stimulus released scant IL6 activity. IFN gamma, IL2, or PDGF did not augment IL6 release from EC. LPS, lipid A, and TNF increased IL6 release modestly (5 to 20-fold), while recombinant IL1s (rIL1s) stimulated this process 100 to 400-fold. Differential release of IL6 from EC treated with LPS or rIL1 continued for at least 144 hr. Exposure to LPS or rIL1 caused EC to synthesize IL6 de novo. EC secreted the newly synthesized IL6 into the supernatant, rather than retaining it within or bound to cells. EC accumulated IL6 mRNA after 3 hr of exposure to rIL1. However, we could only detect IL6 message in cells incubated with LPS under "superinduction" conditions with cycloheximide, consistent with lower levels of IL6 biological activity in response to LPS compared to IL1 stimulation. We propose that local production of IL6 by vascular EC, which comprise the barrier between tissues and the blood, may influence regional immune and inflammatory responses.
Loppnow
H
H
Department of Medicine, Tufts University, Boston, Massachusetts 02111.
Libby
P
P
D000937:Antigen-Antibody Reactions; D015152:Blotting, Northern; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000276:immunology / Q000494:pharmacology*; D015850:Interleukin-6; D007378:Interleukins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D011112:Polymyxin B / Q000494:pharmacology; D011233:Precipitin Tests; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins; D013997:Time Factors
D007375:Interleukin-1; D015850:Interleukin-6; D007378:Interleukins; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D011994:Recombinant Proteins; D011112:Polymyxin B