High glucose enhances the gene expression of interleukin-8 in human endothelial cells, but not in smooth muscle cells: possible role of interleukin-8 in diabetic macroangiopathy

Abstract

Several large prospective epidemiological investigations have disclosed that coronary artery disease is the main cause of morbidity and death in patients with diabetes mellitus. The Multiple Risk Factor Intervention Trial [1] revealed that the mortality rate for coronary artery disease and cardiovascular disease such as cerebral infarction and arteriosclerosis obliterans was three times higher in diabetic men than in non-diabetic men.However, the exact cellular and molecular mechanism for increased risk of these atherosclerotic vascular diseases in diabetic patients remains unclear. Atherosclerosis is described as a response of the artery wall to initiating agents followed by the formation of the atherosclerotic plaque by multiple pathogenic mechanisms [2]. One critical pathological event in the atherosclerotic lesion is the migration of medial smooth muscle cells (SMC) to the intima where these cells proliferate. Various molecules regulating SMC growth are secreted from platelets, monocyte/macrophages, lymphocytes, endothelial cells, and SMC themselves. These cells, in concert with a damaged and/or "activated" endothelium, synthesize and release many kinds of growth factors and cytokines, which lead to the migration and proliferation of SMC, the recruitment of additional blood cells, and the accumulation of lipids. Among proinflammatory cytokines, tumour necrosis factor(TNF)-a, interleukin(IL)-1b, IL-6, and IL-8 are reported to be involved in the pathogenesis of atherosclerosis [3].

Adiponectin Inhibits Endothelial Synthesis of Interleukin-8

“…Those actions include recruitment of neutrophils and T lymphocytes into the subendothelial space, monocyte adhesion to endothelium, 3,4 and migration of vascular smooth muscle cells. 5,6 Macrophage-derived human foam cells contain high amounts of IL-8, 7,8 which can also increase the instability of atherosclerotic plaque through inhibition of tissue inhibitor of metalloproteinase expression. 9 Adipose tissue is now recognized as an endocrine organ.…”

“…6 For experiments, HAECs were cultured with media in the presence or absence of 10 to 30 g/mL human recombinant Adp (BioVendor Laboratory Medicine, Inc) for 24 hours. The HAEC were pretreated with 10 mol/L of a protein kinase A (PKA) inhibitor, Rp-cAMPS, TEA (Rp-cAMP; Calbiochem-Novabiochem AG), 40 mol/L of a PI3 kinase inhibitor, LY294002 hydrochloride (LY294002; Sigma), or vehicle for 1 hour.…”

Pravastatin suppresses the interleukin‐8 production induced by thrombin in human aortic endothelial cells cultured with high glucose by inhibiting the p44/42 mitogen activated protein kinase

“…Northern blot analysis was performed according to the method as previously described (Temaru et al, 1997). Brie¯y, AoEC were cultured with media containing 5.5 mM glucose in the presence or absence of pravastatin (10 mM) in 6 cm culture dishes coated with type-I collagen, and then cells were serum-starved by the media containing 0.5% FCS for 16 h. After stimulation with thrombin, RNA from the AoEC was extracted by ISOGEN (Nippon Gene, Japan).…”

“…Such cellular responses are regulated by growth factors and cytokines such as ®broblast growth factor, platelet derived growth factor, tumour necrosis factor (TNF)-a, interleukin (IL)-1, IL-6, IL-8 and monocyte chemoattractant protein (MCP)-1. We previously reported that in aortic endothelial cells (AoEC) high concentrations of glucose stimulated the IL-8 production, but did not stimulate IL-1, IL-6 and TNF-a production (Urakaze et al, 1996;Temaru et al, 1997). Therefore, we postulated that IL-8 plays some role in the pathogenesis of diabetic angiopathy.…”

“…The administration of pravastatin may be useful for preventing the progression of atherosclerosis even in normolipidaemic patients for whom the increased production of IL-8 from endothelial cells appears to aggravate the atherosclerosis such as diabetic patients (Urakaze et al, 1996;Temaru et al, 1997).…”