title: Tumor necrosis factor-alpha deficiency retards early fatty-streak lesion by influencing the expression of inflammatory factors in apoE-null mice.
abstract: Tumor necrosis factor-alpha (TNF-alpha), a key inflammatory cytokine, plays an important role in atherosclerosis. However, its precise characters in primary stage of the disease remain unclear. To assess the influence of TNF-alpha on inflammatory factors in aorta and liver in apoE and TNF-alpha double mutant (AT) mice, a comparative study on early fatty-streak lesion, the mRNA level of target gene in aorta and liver of adolescent AT and apoE-null (apoE(-/-)) mice were achieved. The characteristics of expression of inflammatory factors, and early fatty-streak lesion relevance were analyzed. The plasma cytokines in 6-week-old AT and apoE(-/-) mice were also measured. Lipid accumulation in the intima of the aorta existed as early as 3 weeks of age in apoE(-/-) mice. Fatty-streak lesion was mild in AT mice but prominent in apoE(-/-) mice, at age of 6 weeks. Furthermore, most interesting findings indicate that mRNA levels of pro-atherosclerotic factors, i.e. IL-1beta, IFN-gamma, ICAM-1, VCAM-1, MCP-1, GM-CSF and NF-kappaB (p65) were significantly downregulated in AT mice. Whereas IL-2 and IkappaB-alpha were upregulated in aorta of AT mice versus those in apoE(-/-) mice (p<0.01) and the transcript levels of pro-inflammatory cytokines, such as IL-1beta, IFN-gamma, ICAM-1, VCAM-1, MCP-1 and GM-CSF, increased with atherogenesis progression. On the other hand, the expression of these inflammatory factors in the liver displayed somewhat similar fashion to those in the aorta. Moreover, the plasma lipids profile in AT mice showed less pro-atherogenic than that of apoE(-/-) mice. Our data indicated that TNF-alpha deficiency surely, although not completely, retards fatty-streak lesion formation due to downregulated expression of the pro-atherosclerotic inflammatory factors in the present circumstance.
authors.affiliation: The Key Laboratory of Animal Resistant Biology of Shandong, College of Life Sciences, Shandong Normal University, Jinan, Shandong 250014, PR China.
authors.forename: Ning
authors.initials: N
authors.lastname: Xiao
authors.forename: Miao
authors.initials: M
authors.lastname: Yin
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.forename: Xuebin
authors.initials: X
authors.lastname: Qu
authors.forename: Hui
authors.initials: H
authors.lastname: Du
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Sun
authors.forename: Liufeng
authors.initials: L
authors.lastname: Mao
authors.forename: Guocheng
authors.initials: G
authors.lastname: Ren
authors.forename: Cong
authors.initials: C
authors.lastname: Zhang
authors.forename: Yue
authors.initials: Y
authors.lastname: Geng
authors.forename: Liguo
authors.initials: L
authors.lastname: An
authors.forename: Jie
authors.initials: J
authors.lastname: Pan
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency* / Q000378:metabolism; D050197:Atherosclerosis / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D005786:Gene Expression Regulation; D005838:Genotype; D018836:Inflammation Mediators / Q000378:metabolism*; D008055:Lipids / Q000097:blood; D008099:Liver / Q000378:metabolism; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000172:deficiency*
chemical_list: D001057:Apolipoproteins E; D018836:Inflammation Mediators; D008055:Lipids; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha