Expression of interleukin-6 in atherosclerotic lesions of male ApoE-knockout mice: inhibition by 17beta-estradiol.
Increased levels of interleukin-6 (IL-6) have been proposed to contribute to a number of pathological disorders, including osteoporosis and Alzheimer's disease. In human atherosclerotic lesions, IL-6 protein and mRNA have been detected, although the role of IL-6 in plaque formation is unknown. We have examined the expression pattern of IL-6 mRNA and secreted protein in male apolipoprotein E-knockout (apoE-KO) mice aortas. Furthermore, we have evaluated the effects of 17beta-estradiol (E2), a vasculoprotective sex steroid hormone, on the secretion of this inflammatory cytokine from isolated male apoE-KO mice aortas. The expression of IL-6 mRNA was detected by reverse transcription-polymerase chain reaction in the apoE-KO mouse aortas but not in the aortas of age-matched control mice. Similarly, the secretion of IL-6 protein from isolated apoE-KO aortic segments was significantly greater than that from aortas of age-matched control animals. The secretion of IL-6 from isolated aortic rings of apoE-KO mice ranging in age from 6 to 48 weeks showed a significant, positive correlation with percent lesion area measured in the same tissue. Immunohistochemical staining of apoE-KO mouse aortic tissue sections demonstrated colocalization of IL-6 expression with macrophages. Treatment of male apoE-KO mice with E2 for 3 weeks resulted in a statistically significant 50% reduction in IL-6 secretion from ex vivo aortic tissue segments. There was no significant change in total serum cholesterol and triglyceride levels in the E2-treated group compared with placebo-treated controls. These data demonstrate that (1) IL-6 mRNA and protein are expressed in the atherosclerotic plaques of apoE-KO mice aortas and (2) IL-6 production is suppressed by E2 treatment, which may contribute to the antiatherosclerotic effects of E2 in the apoE-KO mouse model of atherosclerosis.
Sukovich
D A
DA
Department of Cardiovascular Research, Berlex Biosciences, Richmond, Calif 94804-0099, USA. Drew_Sukovich@Berlex.com
Kauser
K
K
Shirley
F D
FD
DelVecchio
V
V
Halks-Miller
M
M
Rubanyi
G M
GM
D000818:Animals; D001011:Aorta / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D001161:Arteriosclerosis / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood; D004958:Estradiol / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D015850:Interleukin-6 / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D008264:Macrophages / Q000737:chemistry; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009924:Organ Culture Techniques; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D012194:RNA-Directed DNA Polymerase; D014280:Triglycerides / Q000097:blood
D001057:Apolipoproteins E; D015850:Interleukin-6; D012333:RNA, Messenger; D014280:Triglycerides; D004958:Estradiol; D002784:Cholesterol; D012194:RNA-Directed DNA Polymerase