Production of the cytokines interleukin 1 and 6 by murine brain microvessel endothelium and smooth muscle pericytes.
Murine brain microvessel endothelial cells and smooth muscle/pericytes (SM/P) cells were cultured from newborn BALB/c (normal strain) and SJL/j (autoimmune-prone strain) mice. These cells were evaluated for their ability to produce interleukin (IL)-1 and IL-6 cytokines. The expression of mRNA for IL-1 and IL-6 was shown in highly purified BALB/c endothelial cells and SM/P cells using polymerase chain reaction with specific primers for IL-1 alpha, IL-1 beta and IL-6. IL-6 but not IL-1 mRNA was detected in unstimulated SJL/j brain microvessel cells. The presence of IL-1 and IL-6 mRNA in the BALB/c brain microvessel endothelial cells and SM/P was confirmed by in situ hybridization. By D10.G4.1 assay, unstimulated BALB/c endothelial cells were shown to produce active IL-1 to a higher degree than SM/P. By B9 bioassay, a low amount of active IL-6 was detected in the supernatant of endothelial cells and SM/P. The production of IL-1 and IL-6 in the bioassays was upregulated by lipopolysaccharide (LPS) activation of the cells in a time- and dose-dependent way. IL-6 production was also shown to be upregulated by IL-1 beta activation of the cells. Brain microvessel endothelial cells of SJL/j origin released equivalent amounts of IL-6 compared to endothelial cells of BALB/c origin. However, the production of IL-6 was markedly higher in SM/P of SJL/j origin than in those of BALB/c origin. These observations, together with our previous data showing that brain microvessel SM/P cells produce GM-CSF, emphasize the possibility for active participation of brain microvasculature SM/P as well as endothelium in inflammatory reactions of the central nervous system.
Department of Pathology, University of Iowa College of Medicine, Iowa City 52242-1181.
Z
Z
Fabry
K M
KM
Fitzsimmons
J A
JA
Herlein
T O
TO
Moninger
M B
MB
Dobbs
M N
MN
Hart
D000818:Animals; D001483:Base Sequence; D001681:Biological Assay; D001921:Brain / Q000098:blood supply*; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology*; D005260:Female; D015870:Gene Expression; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009130:Muscle, Smooth / Q000166:cytology / Q000276:immunology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D015854:Up-Regulation
D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger