scholarly journals Impaired skeletal development in interleukin-6–transgenic mice: A model for the impact of chronic inflammation on the growing skeletal system

2006 ◽  
Vol 54 (11) ◽  
pp. 3551-3563 ◽  
Author(s):  
Fabrizio De Benedetti ◽  
Nadia Rucci ◽  
Andrea Del Fattore ◽  
Barbara Peruzzi ◽  
Rita Paro ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Chronic Inflammation ◽  
Interleukin 6 ◽  
Skeletal Development ◽  
Skeletal System ◽  
The Impact

scholarly journals Interleukin 7 Transgenic Mice Develop Chronic Colitis with Decreased Interleukin 7 Protein Accumulation in the Colonic Mucosa

1998 ◽  
Vol 187 (3) ◽  
pp. 389-402 ◽  
Author(s):  
Mamoru Watanabe ◽  
Yoshitaka Ueno ◽  
Tomoharu Yajima ◽  
Susumu Okamoto ◽  
Tatsuhiko Hayashi ◽  
...  
Keyword(s):  
T Cells ◽  
Epithelial Cells ◽  
Transgenic Mice ◽  
Chronic Inflammation ◽  
Colonic Mucosa ◽  
Flow Cytometric Analysis ◽  
Receptor Expression ◽  
Protein Accumulation ◽  
Chronic Colitis ◽  
Interleukin 7

We have demonstrated that intestinal epithelial cells produce interleukin 7 (IL-7), and IL-7 serves as a potent regulatory factor for proliferation of intestinal mucosal lymphocytes expressing functional IL-7 receptor. To clarify the mechanism by which locally produced IL-7 regulates the mucosal lymphocytes, we investigated IL-7 transgenic mice. Here we report that transgenic mice expressing murine IL-7 cDNA driver by the SRα promoter developed chronic colitis in concert with the expression of SRα/IL-7 transgene in the colonic mucosa. IL-7 transgenic but not littermate mice developed chronic colitis at 4–12 wk of age, with histopathological similarity to ulcerative colitis in humans. Southern blot hybridization and competitive PCR demonstrated that the expression of IL-7 messenger RNA was increased in the colonic mucosal lymphocytes but not in the colonic epithelial cells. IL-7 protein accumulation was decreased in the goblet cell–depleted colonic epithelium in the transgenic mice. Immunohistochemical and cytokine production analysis showed that lymphoid infiltrates in the lamina propria were dominated by T helper cell type 1 CD4+ T cells. Flow cytometric analysis demonstrated that CD4+ intraepithelial T cells were increased, but T cell receptor γ/δ T cells and CD8α/α cells were not increased in the area of chronic inflammation. Increased IL-7 receptor expression in mucosal lymphocytes was demonstrated in the transgenic mice. These findings suggest that chronic inflammation in the colonic mucosa may be mediated by dysregulation of colonic epithelial cell–derived IL-7, and this murine model of chronic colitis may contribute to the understanding of the pathogenesis of human inflammatory bowel disease.

The Impact of Cardiopulmonary Bypass on Systemic Interleukin-6 Release, Cerebral Nuclear Factor-kappa B Expression, and Neurocognitive Outcome in Rats

2010 ◽  
Vol 110 (2) ◽  
pp. 312-320 ◽  
Author(s):  
Bettina Jungwirth ◽  
Barbara Eckel ◽  
Manfred Blobner ◽  
Kristine Kellermann ◽  
Eberhard F. Kochs ◽  
...  
Keyword(s):  
Cardiopulmonary Bypass ◽  
Interleukin 6 ◽  
Nuclear Factor Kappa B ◽  
Nuclear Factor ◽  
Neurocognitive Outcome ◽  
Nuclear Factor Kappa ◽  
The Impact

scholarly journals THE IMPACT OF G174C POLYMORPHISM ON INTERLEUKIN-6 GENE IS ASSOCIATED WITH THE ONSET AGE IN PATIENTS WITH CORONARY ARTERY DISEASE

2011 ◽  
Vol 57 (14) ◽  
pp. E1596
Author(s):  
George Hatzis ◽  
Dimitris Tousoulis ◽  
Charalambos Antoniades ◽  
Antigoni Miliou ◽  
Nikolaos Papageorgiou ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Interleukin 6 ◽  
Onset Age ◽  
Artery Disease ◽  
The Impact

scholarly journals Creating and validating a DNA methylation-based proxy for Interleukin-6

2020 ◽  
Author(s):  
Anna J Stevenson ◽  
Danni A Gadd ◽  
Robert Francis Hillary ◽  
Daniel L. McCartney ◽  
Archie Campbell ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cognitive Functioning ◽  
Cognitive Ability ◽  
Chronic Inflammation ◽  
Interleukin 6 ◽  
Epigenetic Mechanism ◽  
Inverse Association ◽  
Age Related ◽  
Independent Test ◽  
Methylation Score

Chronic inflammation is a pervasive feature of ageing and may be linked to age-related cognitive decline. However, population studies evaluating its relationship with cognitive functioning have produced heterogeneous results. A potential reason for this is the variability of inflammatory mediators which could lead to misclassifications of individuals' persisting levels of inflammation. The epigenetic mechanism DNA methylation has shown utility in indexing environmental exposures and could potentially be leveraged to provide proxy signatures of chronic inflammation. We conducted an elastic net regression of interleukin-6 (IL-6) in a cohort of 895 older adults (mean age: 69 years) to develop a DNA methylation-based predictor. The predictor was tested in an independent cohort (n=7,028 [417 with measured IL-6], mean age: 51 years).We examined the association between the DNA methylation IL-6 score and serum IL-6, its association with age and established correlates of circulating IL-6, and with cognitive ability. A weighted score from 12 DNA methylation sites optimally predicted IL-6 (independent test set R2=5.1%). In the independent test cohort, both measured IL-6, and the DNA methylation proxy, increased as a function of age (serum IL-6: n=417, β=0.02, SE=0.004 p=1.3x10-7; DNAm IL-6 score: n=7,028, β=0.02, SE=0.0009, p<2x10-16). Serum IL-6 was not found to associate with cognitive ability (n=417, β=-0.06, SE=0.05, p=0.19); however, an inverse association was identified between the DNA methylation score and cognitive functioning (n=7,028, β=-0.14, SE=0.02, pFDR=1.5x10-14). These results suggest DNA methylation-based predictors can be used as proxies for inflammatory markers, potentially allowing for reliable insights into the relationship between chronic inflammation and pertinent health outcomes.

scholarly journals Creating and Validating a DNA Methylation-Based Proxy for Interleukin-6

2021 ◽  
Author(s):  
Anna J Stevenson ◽  
Danni A Gadd ◽  
Robert F Hillary ◽  
Daniel L McCartney ◽  
Archie Campbell ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cognitive Functioning ◽  
Chronic Inflammation ◽  
Interleukin 6 ◽  
Inverse Association ◽  
Generation Scotland ◽  
Independent Test ◽  
Lothian Birth Cohort ◽  
Weighted Score ◽  
The Relationship

Abstract Background Studies evaluating the relationship between chronic inflammation and cognitive functioning have produced heterogeneous results. A potential reason for this is the variability of inflammatory mediators which could lead to misclassifications of individuals’ persisting levels of inflammation. DNA methylation (DNAm) has shown utility in indexing environmental exposures and could be leveraged to provide proxy signatures of chronic inflammation. Method We conducted an elastic net regression of interleukin-6 (IL-6) in a cohort of 875 older adults (Lothian Birth Cohort 1936; mean age: 70 years) to develop a DNAm-based predictor. The predictor was tested in an independent cohort (Generation Scotland; N = 7028 [417 with measured IL-6], mean age: 51 years). Results A weighted score from 35 CpG sites optimally predicted IL-6 in the independent test set (Generation Scotland; R2 = 4.4%, p = 2.1 × 10−5). In the independent test cohort, both measured IL-6 and the DNAm proxy increased with age (serum IL-6: n = 417, β = 0.02, SE = 0.004, p = 1.3 × 10−7; DNAm IL-6 score: N = 7028, β = 0.02, SE = 0.0009, p &lt; 2 × 10−16). Serum IL-6 did not associate with cognitive ability (n = 417, β = −0.06, SE = 0.05, p = .19); however, an inverse association was identified between the DNAm score and cognitive functioning (N = 7028, β = −0.16, SE = 0.02, pFDR &lt; 2 × 10−16). Conclusions These results suggest methylation-based predictors can be used as proxies for inflammatory markers, potentially allowing for further insight into the relationship between inflammation and pertinent health outcomes.

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