IL-20 Is Expressed in Atherosclerosis Plaques and Promotes Atherosclerosis in Apolipoprotein E–Deficient Mice

Abstract

Objective-Atherosclerosis is a chronic inflammatory disease with immune cell infiltration. Various cytokines and chemokines have been characterized as pro-or antiatherogenic factors. belongs to the IL-10 family and is a proinflammatory cytokine involved in the pathogenesis of psoriasis. However, the association between IL-20 and atherosclerosis is undetermined. Therefore, we sought to investigate whether IL-20 is associated with atherosclerosis. A therosclerosis is a chronic inflammatory disease of the arterial wall characterized by the progressive accumulation of lipids, extracellular matrix, and cells, including macrophages, T lymphocytes, and smooth muscle cells. 1 Inflammation plays a major role in atherosclerotic plaque disruption and thrombosis; therefore, it greatly influences the occurrence of coronary syndromes and mortality. [2][3][4] Foam cell macrophages are generally thought to play a major role in the pathology of the disease. 2 Activated macrophages secrete cytokines and chemokines that direct and amplify the local immune response. Inflammatory stimuli include lipoproteins trapped within lesions in which protein and lipid moieties have been chemically modified. Lipid-engorged macrophages, or foam cells, comprise the major volume of the early lesions and are enriched in late-stage lesions as well. 3,5 In situ studies of human and animal atherosclerotic lesions have identified the increased expression of several chemokines, cytokines, and tissue-remodeling and lipid metabolism genes. 6 Antibodies to oxidized low-density lipoprotein (Ox-LDL) epitopes and increases in circulating proinflammatory cytokines correlate with vascular disease. 7 In addition, exposure to OxLDL alters the transcription response of macrophages to inflammatory stimuli. 8 These studies implicate activated macrophages and other inflammatory cells in the development and progression of atherosclerosis. Methods and Results-WeAngiogenesis is also crucial in the progression of atherosclerosis plaque formation. The clinical importance of the neovascularization of plaque has been demonstrated by a higher prevalence of neovascularization in lesions with plaque rupture, mural hemorrhage, or unstable angina. 9 Therefore, factors that stimulate plaque angiogenesis also contribute to plaque disruption, which is responsible for myocardial infarction and ischemic stroke. Angiogenesis inhibitors such as endostatin reduce intimal neovascularization and plaque growth in apolipoprotein E-deficient (apoE Ϫ/Ϫ ) mice. 10 This evidence further supports the importance of angiogenesis in the pathogenesis of atherosclerosis. See page 1929An imbalance between the demand and supply of oxygen is another key factor for the development of atherosclerotic lesions. In vivo, zones of hypoxia occur within the atherosclerotic plaque through the mechanism of impaired oxygen diffusion capacity caused by the thickness of the lesion, together with high oxygen IL-10, important in atherosclerotic lesion formation and stability, is a protective factor against the e...

A novel transcript of mouse interleukin-20 receptor acts on glomerular mesangial cells as an aggravating factor in lupus nephritis

“…In response to ligand binding, the CRF2 proteins form heterodimers, leading to cytokine-specific cellular responses. The biological effects of these three cytokines appear quite distinct: immune activity with IL-19, [7][8][9][10][11][12] skin biology, atherosclerosis and synovial biology in rheumatoid arthritis with IL-20, [13][14][15][16][17][18][19][20] and tumor apoptosis with IL-24. [21][22][23][24][25][26] Within the CRF2 family, only IL-22 binding protein was identified as a decoy receptor functioning as a naturally occurring, highly specific IL-22 antagonist in both humans [27][28][29] and mice.…”

Structural basis for receptor sharing and activation by interleukin-20 receptor-2 (IL-20R2) binding cytokines

“…However, IL-19 Tg mice were reported to exhibit a normal skin phenotype, which is consistent with IL-19's unique receptor specificity. IL-20 is also implicated in rheumatoid arthritis (RA) (14) and atherosclerosis (15). IL-20 also exhibits arteriogenic/angiogenic properties and may be important for treating ischemic disease (16).…”

Anti–IL-20 Monoclonal Antibody Alleviates Inflammation in Oral Cancer and Suppresses Tumor Growth

“…We previously showed (26,28) that IL-20 not only promoted angiogenesis but also increased tumor vascularization. Moreover, IL-20 is regulated by hypoxia and contributes to brain injury in an ischemic stroke model, which indicates that IL-20 is a promoting factor in the inflammation-associated disease (29).…”

“…It acts on multiple cell types by activating a heterodimer receptor complex of either IL-20R1/IL-20R2 or IL-22R1/IL-20R2 (21). It is also involved in various inflammatory diseases, such as psoriasis (22,23), rheumatoid arthritis (24,25), atherosclerosis (26), and renal failure (27).…”