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- Anthoni, M, et al.
(author)
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Smad3 regulates dermal cytokine and chemokine expression and specific antibody production in murine responses to a respiratory chemical sensitizer
- 2010
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In: International archives of allergy and immunology. - : S. Karger AG. - 1423-0097 .- 1018-2438. ; 151:2, s. 155-167
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Journal article (peer-reviewed)abstract
- <i>Background:</i> The cytokine transforming growth factor-β(TGF-β) has important regulatory roles in the immune system. To investigate the role of intact TGF-β signaling during the contact hypersensitivity (CHS) response to a respiratory allergen, we exposed Smad3–/– mice to topical trimellitic anhydride (TMA). <i>Methods:</i> CHS was induced by topical application of TMA. The swelling of the TMA-exposed ears was analyzed, and lymph node, ear tissue and skin biopsies were collected for RNA isolation, histology and histochemical analyses. Lymph node cell proliferation was measured and blood samples were collected for analysis of TMA-specific immunoglobulin. <i>Results:</i> Topical TMA exposure resulted in increased mRNA expression of proinflammatory and suppressive cytokines (IL-1β, TNF-α, IL-6, IFN-γ, IL-4, IL-10, IL-17, IL-23, TGF-β), chemokines (CXCL9, CXCL10, CCL24) and chemokine receptors (CCR7, CCR8, CXCR2), increased numbers of CD3+ T cells in ear tissue, and lymphadenopathy in the Smad3–/– mice. The IL-10 result was confirmed at the protein level by immunohistochemistry. However, the ear-swelling response and infiltration of eosinophils, F4/80+ cells, CD11c+ cells and mast cells were similar in the Smad3–/– mice compared to their wild-type (WT) siblings. While TMA-specific IgE was induced equally in the WT and Smad3–/– mice, the concentration of TMA-specific IgG2a was significantly lower in the Smad3–/– mice. <i>Conclusions:</i> The Smad3 molecule contributes significantly to the regulation of the cytokine and chemokine network during the CHS response to TMA. The lack of Smad3 resulted in a potent Th2 shift, confirmed by strongly impaired IgG2a levels.
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- Graner, M., et al.
(author)
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Cardiac steatosis in patients with dilated cardiomyopathy
- 2014
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In: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 100:14
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Journal article (peer-reviewed)abstract
- Objective Ectopic fat accumulation within and around the heart has been related to increased risk of heart disease. Limited data exist on cardiac adiposity in subjects with dilated cardiomyopathy (DCM). The aim of the study was to examine the components of cardiac steatosis and their relationship to LV structure and function in non-diabetic DCM patients. Methods Myocardial and hepatic triglyceride (TG) contents were measured with 1.5 T magnetic resonance spectroscopy (MRS), and LV function, visceral adipose (VAT) and abdominal subcutaneous tissue (SAT), epicardial and pericardial fat by MRI in 10 non-diabetic men with DCM and in 20 controls. Results In face of comparable intra-abdominal fat depots, myocardial TG [0.41% (0.21-2.19) vs 0.86% (0.31-2.24), p=0.038] was markedly lower and epicardial (895 mm(2)+/- 110 vs 664 mm(2)+/- 180, p=0.002) and pericardial fat [2173 mm(2) (616-3673) vs 1168 mm(2) (266-2319), p=0.039] depots were larger in patients with DCM compared with controls. In subjects with DCM, the LV global function index was decreased to a greater extent than the LV EF [21%+/- 6 vs 34% (16-40)]. Conclusions Myocardial TG content decreased and epicardial and pericardial fat depots increased in non-diabetic subjects with DCM. Although recognised as a site of ectopic fat accumulation, the derangement of myocardial TG seems to play a specific role in the myocardial energy metabolism in congestive heart failure.
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