In patients with obesity and diabetes mellitus, abnormal production of inflammatory factors may result in cardiovascular dysfunction. In the current study, we tested the impact of CD1d-mediated innate immune responses on the expression and activation of NFκB in the hearts of adipose diabetic (db/db) mice. Splenocytes from adult db/db and CD1d-knockout mice of both genders and their wildtype, C57BL/6 and Balb/C counterparts were examined for tumor necrosis factor (TNF)-α and TNF-α receptor type 1. The percentage of natural killer T (NKT) cells in CD3+ T cells was compared with that in nondiabetic control mice. Despite the absence of inflammatory infiltrates, the hearts of db/db mice showed alterations in TNF-α receptor-1 and NFκB activity, including increased expression of both the NFκB p52 and p65 subunits. In the hearts of CD1d-knockout mice, p52 expression was reduced, while p65 expression remained largely unchanged. On echocardiography, the ratio of E to A transmitral flow velocities (an indicator of diastolic function) was significantly decreased in db/db mice after they swam for 30 minutes. These results provide evidence for CD1d-mediated NFκB activation and diastolic dysfunction in the hearts of db/db mice. Therefore, CD1d-associated abnormalities of innate immune responses and TNF-α production in splenic tissue may contribute to NFκB activation and cardiac dysfunction in type 2 diabetes. Copyright © by BIOLIFE, s.a.s.

CD1d-associated expression of NF-κB and cardiac dysfunction in diabetic and obese mice

Madonna R.;
2013

Abstract

In patients with obesity and diabetes mellitus, abnormal production of inflammatory factors may result in cardiovascular dysfunction. In the current study, we tested the impact of CD1d-mediated innate immune responses on the expression and activation of NFκB in the hearts of adipose diabetic (db/db) mice. Splenocytes from adult db/db and CD1d-knockout mice of both genders and their wildtype, C57BL/6 and Balb/C counterparts were examined for tumor necrosis factor (TNF)-α and TNF-α receptor type 1. The percentage of natural killer T (NKT) cells in CD3+ T cells was compared with that in nondiabetic control mice. Despite the absence of inflammatory infiltrates, the hearts of db/db mice showed alterations in TNF-α receptor-1 and NFκB activity, including increased expression of both the NFκB p52 and p65 subunits. In the hearts of CD1d-knockout mice, p52 expression was reduced, while p65 expression remained largely unchanged. On echocardiography, the ratio of E to A transmitral flow velocities (an indicator of diastolic function) was significantly decreased in db/db mice after they swam for 30 minutes. These results provide evidence for CD1d-mediated NFκB activation and diastolic dysfunction in the hearts of db/db mice. Therefore, CD1d-associated abnormalities of innate immune responses and TNF-α production in splenic tissue may contribute to NFκB activation and cardiac dysfunction in type 2 diabetes. Copyright © by BIOLIFE, s.a.s.
Madonna, R.; Wu, H.; Shelat, H.; Geng, Y. -J.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11568/1021798
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