Intramuscular gene transfer of interleukin-10 cDNA reduces atherosclerosis in apolipoprotein E-knockout mice.
Atherosclerosis has a close relationship to inflammation, particularly T helper type 1 lymphocyte (Th1) response. Interleukin-10 (IL-10), is thought to suppress Th1 response. To target therapeutic strategy for atherosclerosis, we tested whether IL-10 gene transfer suppresses atherosclerosis in apolipoprotein E-knockout (apoE-KO) mice. Four-week-old apoE-KO mice were divided into two groups and either murine IL-10 cDNA plasmid or empty control vector was transferred to the femoral muscle with the use of Hemagglutinating virus of Japan (HVJ)-liposome. At 1 week after transfection, high cholesterol diet was started and continued for 8 weeks. After euthanasia, histological studies of atherosclerotic lesions and quantitative RT-PCR for Th1 cytokines (IL-12 and IFN-gamma) in spleens were performed. IL-10 cDNA gene transfer to the muscle increased plasma IL-10 levels and depressed expression of Th1 cytokines without changing plasma cholesterol levels. IL-10 gene transfer significantly reduced the atherosclerotic plaque area and the macrophage infiltrated area. IL-12 and IFN-gamma mRNA expressions in spleens and plasma IFN-gamma levels were decreased by IL-10 gene transfer. Therefore, IL-10 gene transfer changed the Th1 response and suppressed atherosclerotic lesion formation in apoE-KO mice. IL-10 could be a new target as a therapeutic tool for the treatment of atherosclerosis.
Namiki
Masayuki
M
Department of Internal Medicine, Division of Cardiovascular and Respiratory Medicine, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, 650-0017, Kobe, Japan.
Kawashima
Seinosuke
S
Yamashita
Tomoya
T
Ozaki
Masanori
M
Sakoda
Tsuyoshi
T
Inoue
Nobutaka
N
Hirata
Ken-Ichi
K
Morishita
Ryuichi
R
Kaneda
Yasufumi
Y
Yokoyama
Mitsuhiro
M
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D001161:Arteriosclerosis / Q000628:therapy*; D018076:DNA, Complementary; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D007371:Interferon-gamma / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics*; D018664:Interleukin-12 / Q000235:genetics; D008081:Liposomes; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010957:Plasmids; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D029082:Sendai virus / Q000235:genetics
D001057:Apolipoproteins E; D018076:DNA, Complementary; D008081:Liposomes; D012333:RNA, Messenger; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma