PPARδ inhibits IL-1β-stimulated proliferation and migration of vascular smooth muscle cells via up-regulation of IL-1Ra

Kim, H. J.; Kim, M. Y.; Hwang, Jae Joon; Lee, J. H.; Chang, Ki Churl; Kim, J. H.; Han, Chang Woo; Seo, Han Geuk

doi:10.1007/s00018-010-0328-4

Cited by 40 publications

(39 citation statements)

References 59 publications

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“…Taken together, these data strongly suggest that the decrease in macrophage viability after TG treatment was due to activation of the apoptotic pathway. IL-1β is a cytokine produced by activated macrophages and plays a key role during inflammatory reactions, cell proliferation/differentiation, and apoptosis in atherosclerosis (28)(29)(30). Interestingly, we found a gradual decrease in IL-1β expression in a TG dose-dependent manner ( Fig.…”

Section: Tg Downregulates Il-1β Expressionmentioning

confidence: 63%

Increased expression of interleukin-1β in triglyceride-induced macrophage cell death is mediated by p38 MAP kinase

et al. 2012

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Section: Tg Downregulates Il-1β Expressionmentioning

confidence: 63%

Increased expression of interleukin-1β in triglyceride-induced macrophage cell death is mediated by p38 MAP kinase

et al. 2012

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“…In addition, both IL-1␤ and IL-18 have been shown to induce increased collagen production and proliferation of fibroblasts from various origins (12,16,33). Furthermore, studies have demonstrated that both cytokines can induce vascular smooth muscle proliferation and migration (6,23,54). Thus it is not unlikely that the lack of muscularization and fibrosis observed in ASC Ϫ/Ϫ mice is related to impaired IL-18 and IL-1␤ production.…”

Section: Discussionmentioning

confidence: 99%

Absence of the inflammasome adaptor ASC reduces hypoxia-induced pulmonary hypertension in mice

Cero

Hillestad

Sjaastad

et al. 2015

American Journal of Physiology-Lung Cellular and Molecular Phys

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Pulmonary hypertension is a serious condition that can lead to premature death. The mechanisms involved are incompletely understood although a role for the immune system has been suggested. Inflammasomes are part of the innate immune system and consist of the effector caspase-1 and a receptor, where nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3 (NLRP3) is the best characterized and interacts with the adaptor protein apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC). To investigate whether ASC and NLRP3 inflammasome components are involved in hypoxiainduced pulmonary hypertension, we utilized mice deficient in ASC and NLRP3. Active caspase-1, IL-18, and IL-1␤, which are regulated by inflammasomes, were measured in lung homogenates in wild-type (WT), ASC Ϫ/Ϫ , and NLRP3 Ϫ/Ϫ mice, and phenotypical changes related to pulmonary hypertension and right ventricular remodeling were characterized after hypoxic exposure. Right ventricular systolic pressure (RVSP) of ASC Ϫ/Ϫ mice was significantly lower than in WT exposed to hypoxia (40.8 Ϯ 1.5 mmHg vs. 55.8 Ϯ 2.4 mmHg, P Ͻ 0.001), indicating a substantially reduced pulmonary hypertension in mice lacking ASC. Magnetic resonance imaging further supported these findings by demonstrating reduced right ventricular remodeling. RVSP of NLRP3Ϫ/Ϫ mice exposed to hypoxia was not significantly altered compared with WT hypoxia. Whereas hypoxia increased protein levels of caspase-1, IL-18, and IL-1␤ in WT and NLRP3 Ϫ/Ϫ mice, this response was absent in ASC Ϫ/Ϫ mice. Moreover, ASC Ϫ/Ϫ mice displayed reduced muscularization and collagen deposition around arteries. In conclusion, hypoxia-induced elevated right ventricular pressure and remodeling were attenuated in mice lacking the inflammasome adaptor protein ASC, suggesting that inflammasomes play an important role in the pathogenesis of pulmonary hypertension.inflammation; innate immunity; pulmonary vasculature PULMONARY HYPERTENSION can be a life-threatening condition leading to right-sided heart failure and premature death (5, 40). The pathogenesis of the various forms of pulmonary hypertension is not fully known, and insight into disease mechanisms is important for the development of improved treatment options for this severe condition. The role and importance of inflammation and immune activation in the development of pulmonary hypertension are not fully understood; however, inflammation has emerged as an important player. Clinically, increased circulating levels of IL-1␤ and IL-18 have been observed in patients with pulmonary arterial hypertension, indicating that inflammasomes can be activated in this condition (18,41). It is well known that innate immunity is activated in response to infection. However, in the last decade, new knowledge has emerged demonstrating that inflammatory pathways can also be activated as a result of cellular stress during sterile inflammation and that these inflammatory responses involve activation of inflammasomes (27). Inflammasome...

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“…In vitro studies demonstrated that IL-1␤ increases the expression of cell adhesion molecules (295), MCP-1 (156), and lipocalin-2 (30) in vascular SMCs. In addition, it stimulates the migration (299) and proliferation of these cells (128,234). In the ApoE/IL-1␤ double knockout mouse model, IL-1␤ deficiency decreases the severity of atherosclerosis (121,134), further supporting the important role of IL-1␤ in vascular disorders.…”

Section: Adipokines With a Tight Link To Cardiovascular Diseasementioning

confidence: 94%

Inflammation and metabolic dysfunction: links to cardiovascular diseases

Taube

Schlich

Sell

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

201

133

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Abdominal obesity is a major risk factor for cardiovascular disease, and recent studies highlight a key role of adipose tissue dysfunction, inflammation, and aberrant adipokine release in this process. An increased demand for lipid storage results in both hyperplasia and hypertrophy, finally leading to chronic inflammation, hypoxia, and a phenotypic change of the cellular components of adipose tissue, collectively leading to a substantially altered secretory output of adipose tissue. In this review we have assessed the adipo-vascular axis, and an overview of adipokines associated with cardiovascular disease is provided. This resulted in a first list of more than 30 adipokines. A deeper analysis only considered adipokines that have been reported to impact on inflammation and NF-κB activation in the vasculature. Out of these, the most prominent link to cardiovascular disease was found for leptin, TNF-α, adipocyte fatty acid-binding protein, interleukins, and several novel adipokines such as lipocalin-2 and pigment epithelium-derived factor. Future work will need to address the potential role of these molecules as biomarkers and/or drug targets.

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PPARδ inhibits IL-1β-stimulated proliferation and migration of vascular smooth muscle cells via up-regulation of IL-1Ra

Cited by 40 publications

References 59 publications

Increased expression of interleukin-1β in triglyceride-induced macrophage cell death is mediated by p38 MAP kinase

Increased expression of interleukin-1β in triglyceride-induced macrophage cell death is mediated by p38 MAP kinase

Absence of the inflammasome adaptor ASC reduces hypoxia-induced pulmonary hypertension in mice

Inflammation and metabolic dysfunction: links to cardiovascular diseases

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