Interleukin-10 Deficiency Increases Atherosclerosis, Thrombosis, and Low-density Lipoproteins in Apolipoprotein E Knockout Mice

Caligiuri, Giuseppina; Rudling, Mats; Ollivier, Véronique; Jacob, Marie‐Paule; Michel, Jean‐Baptiste; Hansson, Göran K.; Nicoletti, Antonino

doi:10.1007/bf03402102

Cited by 297 publications

(226 citation statements)

References 53 publications

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“…Increased concentration of TGF-β and IL-10 was associated with suppressing pathogenic inflammatory responses, regulating immunity and promoting atherosclerotic plaque stabilization (33). On the contrary, deletion of TGF-β or IL-10 signaling accelerates atherosclerosis and plaque vulnerability (34,35). In the present study, mRNA and protein levels of TGF-β and IL-10 were significantly increased in atherosclerotic plaques in ApoE -/-mice after 6 wks of simvastatin treatment.…”

Section: Tregs Are a Unique Subset Of T Cells Although The Number Ofsupporting

confidence: 40%

Statins Induce the Accumulation of Regulatory T Cells in Atherosclerotic Plaque

Xiao

Zhang

et al. 2012

Mol Med

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+ regulatory T cells (Tregs) mediate immune suppression and prevent autoimmune disorders. Recently, Tregs were found to present in atherosclerotic lesions and play an important role in the progression of atherosclerosis. Statins have immunomodulatory properties, and the effect of statins on atherosclerosis depends in part on their immunomodulatory mechanisms. We sought to determine whether statins exhibit an effect on Tregs in atherosclerotic plaques and in peripheral circulation of patients with acute coronary syndrome (ACS). In an in vivo experiment, we induced atherosclerotic plaques in apolipoprotein E-deficient (ApoE

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Section: Tregs Are a Unique Subset Of T Cells Although The Number Ofsupporting

confidence: 40%

Statins Induce the Accumulation of Regulatory T Cells in Atherosclerotic Plaque

Xiao

Zhang

et al. 2012

Mol Med

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“…The effect of IL-10 on atherogenesis has been studied extensively with different mouse models, all of which demonstrated that IL-10 is an antiatherogenic factor (29)(30)(31). Accordingly, the raised IL-10 plasma levels in A20-haploinsufficient mice may also protect against lesion formation.…”

Section: Discussionmentioning

confidence: 99%

The protective effect of A20 on atherosclerosis in apolipoprotein E-deficient mice is associated with reduced expression of NF-κB target genes

Wolfrum

Teupser

Tan

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Up-regulation of inflammatory responses is considered a driving force of atherosclerotic lesion development. One key regulator of inflammation is the A20 (also called TNF-␣-induced protein 3 or Tnfaip3) gene, which is responsible for NF-B termination and maps to an atherosclerosis susceptibility locus revealed by quantitative trait locus-mapping studies at mouse proximal chromosome 10. In the current study, we examined the role of A20 in atherosclerotic lesion development. At the aortic root lesion size was found to be increased in C57BL/6 (BG) apolipoprotein E-deficient (ApoE ؊/؊ ) mice haploinsufficient for A20, compared with B6 ApoE ؊/؊ controls that expressed A20 normally (60% in males and 23% in females; P < 0.001 and P < 0.05, respectively). In contrast, lesion size was found to be decreased in F 1 (B6؋FVB/N) mice overexpressing A20 by virtue of containing an A20 BAC transgene compared with nontransgenic controls (30% in males, P < 0.001, and 17% in females, P ‫؍‬ 0.02). The increase in lesions in the A20 haploinsufficient mice correlated with increased expression of proatherosclerotic NF-B target genes, such as vascular cell adhesion molecule 1, intercellular adhesion molecule 1, and macrophage-colony-stimulating factor, and elevated plasma levels of NF-B-driven cytokines. These findings suggest that A20 diminishes atherosclerosis by decreasing NF-B activity, thereby modulating the proinflammatory state associated with lesion development.A therosclerosis is a chronic inflammatory disease influenced by many genes, and mouse models are useful for identifying these genes and determining their mechanisms of action. We previously carried out an intercrosses between atherosclerosissensitive apolipoprotein E-deficient (ApoE Ϫ/Ϫ ) C57BL/6 (B6) and atherosclerosis-resistant ApoE Ϫ/Ϫ FVB mice, and by quantitative trait locus mapping identified an atherosclerosissusceptibility locus on proximal chromosome 10 (1, 2). A candidate gene in this region, A20, encodes a broadly expressed cytoplasmic protein that inhibits both TNF-␣-and IL-1␤/Tolllike receptor (TLR)-induced NF-B activation through mediating the destruction of receptor-interacting serine/threonine protein kinase 1 (RIP) and TNF receptor-associated factor 6 in their respective signaling complexes (3, 4). Up-regulation of NF-B activity leads to increased expression of many genes with established roles in atherosclerosis, including cytokines, chemokines, adhesion molecules, acute phase proteins, and regulators of apoptosis and cell proliferation. NF-B terminates its own activation by inducing the expression of I B␣ and A20. A20-deficient (A20 Ϫ/Ϫ ) mice die prematurely because of cachexia and spontaneous inflammation in several organs. This phenotype correlates with the failure to properly terminate TNF-induced NF-B activity in fibroblasts isolated from A20 Ϫ/Ϫ mice (5). We previously determined that A20 derived from B6 and FVB mice differs in a single amino acid residue (E627A; B6 vs. FVB). We showed this finding to be functionally significant by demonstrating...

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“…The anti-inflammatory cytokine IL-10 generates protective signals against atherosclerosis shown in IL-10 deficient mice by increased and in IL-10 transgenic mice by decreased lesion formation [136][137][138]. 15d-PGJ 2 can inhibit IL-10 signaling in a STAT3 dependent and PPAR-c-independent way [139].…”

Section: Inflammatory Cytokines: Agitators Of Inflammatory Milieumentioning

confidence: 99%

Nuclear receptors in macrophages: A link between metabolism and inflammation

Szántó

Röszer

2007

FEBS Letters

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Subclinical inflammation is a candidate etiological factor in the pathogenesis of metabolic syndrome and in the progression of atherosclerosis. A central role for activated macrophages has been elucidated recently as important regulators of the inflammatory process in atherosclerosis. Macrophage differentiation and function can be modulated by a class of transcription factors termed nuclear receptors. These are activated by intermediary products of basic metabolic processes. In this review the contribution of peroxisome proliferator-activated receptors and liver X receptors to macrophage functions in inflammation and lipid metabolism will be discussed in light of their roles in macrophages during atherosclerosis.In the past decade much effort has been made to understand the mechanisms how lipids are handled by macrophages and how inflammation could promote the atherogenic process. Here, we also provide an overview of these two fields.

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Interleukin-10 Deficiency Increases Atherosclerosis, Thrombosis, and Low-density Lipoproteins in Apolipoprotein E Knockout Mice

Cited by 297 publications

References 53 publications

Statins Induce the Accumulation of Regulatory T Cells in Atherosclerotic Plaque

Statins Induce the Accumulation of Regulatory T Cells in Atherosclerotic Plaque

The protective effect of A20 on atherosclerosis in apolipoprotein E-deficient mice is associated with reduced expression of NF-κB target genes

Nuclear receptors in macrophages: A link between metabolism and inflammation

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