Characterization of the cytokine expression profiles of the aorta and liver of young tumor necrosis factor alpha mutant mice

Abstract

Both the aorta and the liver are major organs that play important roles in lipid metabolism, and they are subject to systemic as well as local inflammatory responses in metabolic syndrome. Our previous study indicated that TNFα deficiency influences atherogenesis by reducing inflammation of the aorta. To better understand this phenomenon, the mRNA and protein expression profiles of a panel of cytokines in the aorta and liver of young TNFα-null (TNFα(-/-)) mice were analyzed and compared with age- and gender-matched wild-type (WT) control mice. In the aorta, IL-2 and GM-CSF were up-regulated versus WT mice, while IL-1β, IL-4, IL-6, IL-10, MCP-1, IFN-γ, and the adhesion molecules ICAM-1 and VCAM-1 were down-regulated. In the liver, however, the expressions of NF-κB, IL-1, IL-2, IL-6, IL-10, ICAM-1, and VCAM-1 were significantly up-regulated in TNFα(-/-) mice, while IFN-γ and IL-4 were down-regulated. Out of the 62 cytokines analyzed, 22 in the aorta and 27 in the liver were altered by 2-fivefolds at the protein level in TNFα(-/-) mice. Our data demonstrated that the loss of TNFα function led to various changes in the levels of cytokine expression in these organs at both the transcriptional and translational levels. These results indicated that the changes in cytokine expression patterns in the aorta and the liver may further influence the progression of systemic or local lipid metabolism dysregulation and pathogenesis in animals with TNFα dysfunction representing inflammation-related diseases, such as atherosclerosis and metabolic syndrome.