The regulation of EN-RAGE (S100A12) gene expression in human THP-1 macrophages

Hasegawa, Takamasa; Kosaki, Atsushi; Kimura, Tetsunori; Matsubara, Hiroaki; Mori, Yoshihide; Okigaki, Mitsuhiko; Masaki, Hiroya; Toyoda, Nagaoki; Inoue-Shibata, Megumi; Kimura, Yutaka; Nishikawa, Mitsushige; Iwasaka, Toshiji

doi:10.1016/j.atherosclerosis.2003.08.021

Cited by 71 publications

(50 citation statements)

References 38 publications

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“…S100A12 TG mice displayed pathologic remodeling of the aorta, and cultured aortic vascular smooth muscle cells from TG mice increased the IL-6 production and elevated measures of oxidative stress. We have shown that S100A12 production is induced by IL-6 in human macrophages (30). Thus, S100A12 expression is sufficient to activate pathogenic pathways through the modulation of oxidative stress, inflammation, and vascular remodeling.…”

Section: Discussionmentioning

confidence: 94%

Plasma S100A12 Level Is Associated with Cardiovascular Disease in Hemodialysis Patients

Shiotsu

Mori²,

Nishimura³

et al. 2011

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives S100A12 is an endogenous receptor ligand for advanced glycation end products. Cardiovascular disease remains a major cause of morbidity and mortality in patients with chronic kidney disease. In this study, we report cross-sectional data on 550 hemodialysis patients and assess the relationship between plasma S100A12 level and cardiovascular disease.Design, setting, participants, & measurements A cross-sectional study of 550 maintenance hemodialysis patients was conducted. We investigated the past history of cardiovascular disease and quantified the plasma level of S100A12 protein in all participants.Results Plasma S100A12 level was higher in hemodialysis patients with cardiovascular disease (n ϭ 197; 33.8 Ϯ 28.1 ng/ml) than in those without it (n ϭ 353; 20.2 Ϯ 16.1 ng/ml; P Ͻ 0.001). In multivariate logistic regression analysis, the plasma S100A12 level (odds ratio [OR], 1.28; 95% confidence interval [CI], 1.13 to 1.44; P Ͻ 0.001) was identified as an independent factor associated with the prevalence of cardiovascular disease. The other factors associated with the prevalence of cardiovascular diseases were the presence of diabetes mellitus (OR, 2.81; 95% CI, 1.79 to 4.41; P Ͻ 0.001) and high-sensitivity CRP level (OR, 1.02; 95% CI, 1.00 to 1.05; P ϭ 0.046). Furthermore, the plasma S100A12 level (OR, 1.30; 95% CI, 1.09 to 1.54; P ϭ 0.004) was significantly associated with cardiovascular disease even in hemodialysis patients without diabetes mellitus (n ϭ 348). ConclusionsThese results suggest that the plasma S100A12 protein level is strongly associated with the prevalence of cardiovascular disease in hemodialysis patients.

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Section: Discussionmentioning

confidence: 94%

Plasma S100A12 Level Is Associated with Cardiovascular Disease in Hemodialysis Patients

Shiotsu

Mori²,

Nishimura³

et al. 2011

Clinical Journal of the American Society of Nephrology

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“…Although S100A8/ S100A9 did not respond to the other tested stimuli, S100A12 expression in THP-1 monocytes was significantly enhanced by activation with interleukin-1␤, interferon ␥, and released from thrombin-activated platelets. Previously, interleukin-6 has been found to increase S100A12 expression in THP-1 cells 27 and the ability of S100A12 to be induced by a wide range of stimuli, reflecting several upstreams or upstream inflammatory pathways, could be of importance for its potential as a biomarker in atherosclerotic disease. Previous studies have Figure 2.…”

Section: Discussionmentioning

confidence: 99%

High Levels of S100A12 Are Associated With Recent Plaque Symptomatology in Patients With Carotid Atherosclerosis

Abbas

Aukrust²,

Dahl³

et al. 2012

Stroke

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Background and Purpose-Atherosclerosis is a progressive chronic disease, in which inflammation plays a key role. The calcium-binding proteins calgranulins including S100A8, S100A9, and S100A12 are involved in many cellular activities and pathological processes including inflammation. We therefore hypothesized that calgranulins may be markers of plaque instability in patients with carotid atherosclerosis. Methods-Plasma levels of S100A8/A9 and S100A10 were measured in 159 consecutive patients with high-grade carotid stenosis and in 22 healthy control subjects. The mRNA levels of calgranulins were also measured within the atherosclerotic carotid plaques, and their regulation was analyzed in vitro in monocytes. Results-Our main findings were: (1) plasma levels of S100A12 were significantly higher in patients with carotid atherosclerosis compared with healthy control subjects with the highest levels in patients with the most recent symptoms (ie, within 2 months); (2) plasma levels of S100A8/S100A9 showed a modest increase in patients with symptoms in the previous 2 to 6 months but not in the other patients; (3) mRNA levels of S100A8, S100A9, and S100A12 showed increased expression in atherosclerotic carotid plaques from patients with the most recent symptoms compared with the remaining patients; (4) in THP-1 monocytes, activation of Toll-like receptors 2 and 4 increased mRNA levels of S100A8, S100A9, and S10012 and interleukin-1␤, interferon ␥, and releasate from thrombin-activated platelets significantly enhanced the expression of S100A12. Conclusions-Our findings support a link between calgranulins and atherogenesis and suggest that these mediators, and in particular S100A12, may be related to plaque instability. (Stroke. 2012;43:1347-1353.)

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“…S100A12 may increase expression of osteoblastic genes and facilitate calcification (13). Hyperglycemia might stimulate S100A12 protein production, either directly in granulocytes and monocytes or indirectly via hyperglycemia-produced cytokines (14). Kosakı et al (15) observed that the mean of plasma S100A12 levels was twice as high in the DM group, compared with the non-DM group.…”

Section: Discussionmentioning

confidence: 99%

Serum Heat Shock Protein 70, S100A12 and Matrix Gla Protein in Childhood Obesity and Metabolic Syndrome

Can¹,

Buyukınan²,

Güzelant³

et al. 2016

Van Med J

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Objectives:The primary cause of the metabolic syndrome appears to be obesity that is associated with a low-grade inflammatory state resulting from insulin resistance in both adult and pediatric populations. Heat shock protein 70, S100A12 and matrix Gla protein are involved in chronic inflammatory diseases. We aimed to evaluate the association between these markers and childhood obesity and metabolic syndrome. Materials and Methods:This study was performed with 45 obese children aged 10-15 years and 47 children with metabolic syndrome aged 10-15 years. Serum heat shock protein 70, S100A12 and matrix Gla protein levels were measured by using ELISA method.Results: Serum matrix Gla protein and S100A12 levels in obese subjects were significantly higher than metabolic syndrome groups (p<0.05). However no significant differences were observed in serum high sensitivity Creactive protein (p=0.288) and heat shock protein 70 (p=0.960) levels between metabolic syndrome and obese subjects. There was a significant positive correlation between serum S100A12, matrix Gla protein and heat shock protein 70 levels in both groups. Conclusions:Our findings showed a significant association between heat shock protein 70, S100A12, matrix Gla protein, and obesity and metabolic syndrome. Obesity may be involved in increased risk of developing metabolic syndrome. It might be useful to focus on the roles of these proteins in obesity in accordance with the prevention of the development of metabolic syndrome and other metabolic disorders like diabetes.Key Words: Obesity, metabolic syndrome, heat shock protein 70, S100A12 and matrix Gla protein ÖZET Amaç: Metabolik Sendromun primer nedeni erişkin ve çocuk popülasyonunda insülin rezistansı ile sonuçlanan düşük dereceli inflamasyon ile ilgili obezitedir. Heat şok protein 70,S100A12 ve matriks Gla protein kronik inflamatuar hastalık ile ilgilidir. Çocuk çağı obezitesi ve metabolik sendromun da bu markırları değerlendirmeyi amaçladık. Gereç ve Yöntem:Bu çalışma 10-15 yaş aralığında 45 obez çocuk ve 47 metabolik sendrom'lu çocukta yapıldı. Heat şok protein 70, S100A12 ve matriks Gla protein ELISA metodu kullanılarak ölçüldü. Bulgular:Obez çocuklarda serum matriks Gla protein ve S100A12 seviyeleri metabolik sendrom'lu gruptan anlamlı olarak yüksekti (p<0.05). İlaveten, metabolik sendrom ve obez bireyler arasında serum hsCRP (p=0.288) ve heat şok protein 70 (p=0.960) fark yoktu. Her iki grupta S100A12, matriks Gla protein ve heat şok protein 70 seviyeleri arasında anlamlı pozitif korelasyon vardı.Sonuç: Bulgularımız S100A12, matriks Gla protein ve heat şok protein 70 biyomarkırları metabolik sendrom ve obezite ile anlamlı olarak ilgili olduğunu gösterdi. Obezite metabolik sendrom gelişiminde önemli bir risk faktörüdür. Obezitede bu proteinlerin artışı, metabolik sendrom ve diabet gibi metabolik bozuklukların gelişiminin önlenmesinde ilgi çekici olabilir.

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The regulation of EN-RAGE (S100A12) gene expression in human THP-1 macrophages

Cited by 71 publications

References 38 publications

Plasma S100A12 Level Is Associated with Cardiovascular Disease in Hemodialysis Patients

Plasma S100A12 Level Is Associated with Cardiovascular Disease in Hemodialysis Patients

High Levels of S100A12 Are Associated With Recent Plaque Symptomatology in Patients With Carotid Atherosclerosis

Serum Heat Shock Protein 70, S100A12 and Matrix Gla Protein in Childhood Obesity and Metabolic Syndrome

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