title: CD1d-associated expression of NF-kB and cardiac dysfunction in diabetic and obese mice.
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 NFkB in the hearts of adipose diabetic (db/db) mice. Splenocytes from adult db/db and CD1d-knockout mice of both genders and their wild-type, C57BL/6 and Balb/C counterparts were examined for tumor necrosis factor (TNF)-alpha and TNF-alpha 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-alpha receptor-1 and NFkB activity, including increased expression of both the NFkB 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 NFkB activation and diastolic dysfunction in the hearts of db/db mice. Therefore, CD1d-associated abnormalities of innate immune responses and TNF-alpha production in splenic tissue may contribute to NFkB activation and cardiac dysfunction in type 2 diabetes.
authors.affiliation: The University of Texas Health Science Center, Houston, TX, USA.
authors.forename: R
authors.initials: R
authors.lastname: Madonna
authors.forename: H
authors.initials: H
authors.lastname: Wu
authors.forename: H
authors.initials: H
authors.lastname: Shelat
authors.forename: Y J
authors.initials: YJ
authors.lastname: Geng
mesh_terms: D000818:Animals; D055610:Antigens, CD1d / Q000235:genetics / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009206:Myocardium / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics*; D009765:Obesity / Q000378:metabolism* / Q000503:physiopathology; D021122:Protein Subunits / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics; D013154:Spleen / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D018487:Ventricular Dysfunction, Left / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D055610:Antigens, CD1d; D016328:NF-kappa B; D021122:Protein Subunits; D012333:RNA, Messenger; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha