Internal Medicine I, NDMC Interleukin-1 receptor antagonist in bone marrow-derived cells contributed to the suppression of arterial inflammation and reduced neointimal formation after injury Sarasa Isobe 1 , Kikuo Isoda 1 , Manabu Kitagaki 1 Tomiharu Niida 1 , Harumi Kondo 1 , Koji Akita 1 , Takehiko Kujiraoka 1 , Takumi Toya 1 , and Takeshi Adachi 1 1 Internal Medicine I, National Defense Medical College
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Interleukin-1 receptor antagonist in bone marrow-derived cells
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Internal Medicine I, NDMC
Interleukin-1 receptor antagonist in
bone marrow-derived cells
contributed to the suppression of
arterial inflammation and reduced
neointimal formation after injury
Sarasa Isobe1, Kikuo Isoda1, Manabu Kitagaki1 Tomiharu Niida1, Harumi Kondo1, Koji Akita1, Takehiko Kujiraoka1, Takumi Toya1, and
Takeshi Adachi1
1Internal Medicine I, National Defense Medical College
The authors have no financial conflicts
of interest to disclose concerning the
presentation.
European Society of Cardiology
COI Disclosure
Internal Medicine I, NDMC
Background
Interleukin (IL)-1 is a proinflammatory
cytokine that plays an important role in
inflammation. IL-1 receptor antagonist
(IL-1Ra) negatively regulates IL-1
signaling by blocking the functional
receptor. Thus, IL-1Ra plays an anti-
inflammatory role in inflammation.
Internal Medicine I, NDMC
Deficiency of IL-1Ra promotes neointimal
formation after cuff Injury
WT IL-1Ra-/-
H & E
E. Masson
Isoda et al. Circulation. 2003; 108: 516-518.
Internal Medicine I, NDMC
IL-1Ra is expressed on BM-derived cells as well
as endothelial cells at 7 days after cuff Injury
WT IL-1Ra -/-
Isoda et al. Circulation. 2003; 108: 516-518.
Internal Medicine I, NDMC
Study Aim
To elucidate the role of IL-1Ra
in BM-derived cells in the
development of neointimal
formation after injury.
Internal Medicine I, NDMC
Methods
To disrupt all four isoform of IL-1Ra gene production, a
5.2-kb DNA fragment which contains all the coding
regions for the secreted form of the IL-1Ra was deleted.
Screening of Mice: Southern blot and PCR.
Internal Medicine I, NDMC
Bone marrow cell transplantation
Ra-/->Ra-/-
WT >Ra-/-
WT
Ra-/-
Donor
Recipient Ra-/-
750rad
Internal Medicine I, NDMC
Artery injury
Polyethylene cuff was placed around the femoral artery
(reported by Moroi et al).
vein
artery
Histological analysis
After perfusion, the femoral artery was harvested, frozen in
OCT medium and sectioned.
All samples were stained with Victoria blue-HE, and