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Shinsuke N.,Kyorinkai Murakami Memorial Hospital | Hiroshi I.,Kyorinkai Murakami Memorial Hospital
Autoimmunity | Year: 2013

To identify the effect of an imbalance of Th1/Th2 cytokines on the development of autoimmune glomerulonephritis (lupus nephritis), we studied the modification of pathological changes in diffuse proliferative glomerulonephritis (DPGN) and membranous glomerulonephritis (MGN) in MRL/lpr mice, which are animal models of systemic lupus erythematosus (SLE). Transgenic MRL/lpr mice (Tg) that overexpressed Epstein-Barr virus-induced gene 3 (EBI3) showed almost normal renal function, which was demonstrated by healing of glomerulonephritis upon renal histology, as compared to the wild-type MRL/lpr (Wt) mice. The levels of anti-dsDNA antibodies and IgE decreased in the Tg mice compared to Wt mice. Quantitative real-time PCR indicated an increase in the mRNA levels of FoxP3, and a decrease in that of IFNγ in the splenocytes of Tg mice as compared to Wt mice. In addition, flow cytometric analysis showed an increase in CD4 +CD25+FoxP3+-T cells in the former, as compared to the latter. Our findings suggest that EBI3-overexpression in MRL/lpr mice induces generation of regulatory T cells, which causes suppression of autoimmune and inflammatory reactions by affecting the Th1/Th2 cytokine balance. © 2013 Informa UK Ltd.

Matsumae T.,Kyorinkai Murakami Memorial Hospital | Ueda K.,Kyorinkai Murakami Memorial Hospital | Abe Y.,Fukuoka University | Nishimura S.,Kyorinkai Murakami Memorial Hospital | And 2 more authors.
Hypertension Research | Year: 2010

Increased aortic stiffness is an independent predictor of death from cardiovascular disease in patients with end-stage renal disease (ESRD). Various factors that contribute to carotid-femoral pulse wave velocity (cfPWV) as a surrogate of aortic stiffness have been identified, but determinants of long-term worsening of aortic stiffness remain to be elucidated. To clarify the factors that accelerate aortic stiffness in hemodialysis patients, 148 patients with ESRD on hemodialysis were evaluated. At baseline, cfPWV and ankle-brachial blood pressure index (ABPI) were measured and clinical status including biochemical parameters, with or without hepatitis c virus (HCV) infection, diabetes mellitus (DM), cardiovascular disease, cerebrovascular disease and peripheral arterial disease at baseline, were evaluated. The cfPWV was measured again after a 3-year follow up and the annual change in cfPWV was calculated. The cfPWV decreased in 54 patients, worsened slowly in 47 (annual change in cfPWV ranged from 0 to 0.33 ms-1 per year), and worsened rapidly in 47 patients (annual change in cfPWV was more than 0.33 ms-1 per year). The prevalences of DM, HCV infection and peripheral arterial disease were the highest in the rapid progression group. Univariate analysis showed that age, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), LDL-C/HDL-C ratio, HCV infection, ABPI and number of vasculopathies were significantly associated with annual change in cfPWV. Stepwise regression analysis identified ABPI, LDL-C/HDL-C ratio and HCV infection as independent determinants of worsening of cfPWV. Further studies are needed to investigate the mechanism of HCV-related enhancement of aortic stiffness in ESRD patients. © 2010 The Japanese Society of Hypertension All rights reserved.

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