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*
Department of Medicine, Northwestern University Medical School, Chicago, IL 60611; and
Veteran’s Administration Chicago Health Care System, Lakeside Division, Chicago, IL 60611
Angiogenesis, or new blood vessel growth, is a key process in the
development of synovial inflammation in rheumatoid arthritis (RA).
Integral to this pathologic proliferation are proinflammatory
cytokines. We hypothesized a role for IL-18 as an angiogenic mediator
in RA. We examined the effect of human IL-18 on human microvascular
endothelial cell (HMVEC) migration. IL-18 induced HMVEC migration at 1
nM (p < 0.05). RA synovial fluids potently induced
endothelial cell migration, but IL-18 immunodepletion resulted in a
68 ± 5% decrease in HMVEC migration (p <
0.05). IL-18 appears to act on HMVECs via
v
3 integrin. To test whether IL-18
induced endothelial cell tube formation in vitro, we quantitated the
degree of tube formation on Matrigel matrix. IL-18, 1 or 10 nM,
resulted in a 77% or 87% increase in tube formation compared with
control (p < 0.05). To determine whether IL-18 may
be angiogenic in vivo, we implanted IL-18 in Matrigel plugs in mice,
and IL-18 at 1 and 10 nM induced angiogenesis (p <
0.05). The angiogenesis observed appears to be independent of the
contribution of local TNF-, as evidenced by adding neutralizing
anti-TNF- Ab to the Matrigel plugs. In an alternative in vivo
model, sponges embedded with IL-18 or control were implanted into mice.
IL-18 (10 nM) induced a 4-fold increase in angiogenesis vs the control
(p < 0.05). These findings support a novel
function for IL-18 as an angiogenic factor in RA and may elucidate a
potential therapeutic target for angiogenesis-directed
diseases.
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|
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|
|
|
|
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|
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