%0 Journal Article
%T Activation of transforming growth factor-¦Â1 and early atherosclerosis in systemic lupus erythematosus
%A Michelle Jackson
%A Yasmeen Ahmad
%A Ian N Bruce
%A Beatrice Coupes
%A Paul EC Brenchley
%J Arthritis Research & Therapy
%D 2006
%I BioMed Central
%R 10.1186/ar1951
%X Transforming growth factor (TGF)-¦Â1 is the most potent naturally occurring immunosuppressant [1]; it is produced by all cells of the immune system and plays a fundamental role in controlling proliferation and the fate of cells through apoptosis. In TGF-¦Â1 knockout mice [2] lack of TGF-¦Â1 initiates indiscriminate loss of self-tolerant T cells. Consequential dysregulation of B cell activity leads to production of systemic lupus erythematosus (SLE)-like autoantibodies [3] and development of a lupus-like illness, resulting in early death at 3¨C4 weeks [2]. Preliminary human studies suggest that TGF-¦Â1 expression in SLE may be dysregulated. Production of TGF-¦Â1 by lymphocytes isolated from SLE patients is reduced compared with that in control individuals [4]. Spontaneous polyclonal IgG and autoantibody production can be abrogated by treatment with interleukin-2 and TGF-¦Â1 [5].Atherosclerosis is a major cause of mortality and morbidity in SLE, with 6¨C10% of patients developing premature clinical coronary heart disease [6]. The 'protective cytokine hypothesis', recently reviewed [7], proposes that active TGF-¦Â1 in the vascular wall is required to maintain the normal vascular wall structure and controls the balance between inflammation and extracellular matrix deposition in atherosclerosis. TGF-¦Â1 is an inhibitor of smooth muscle and endothelial cell proliferation [8]. Mice heterozygous for the deletion of the TGF-¦Â1 gene (tgf¦Â1+/-) have a 50% reduction in levels of TGF-¦Â1 in artery walls and, when fed a cholesterol-enriched diet, such mice exhibit marked deposition of lipid in the artery wall as compared with wild-type mice [9]. In experimental models the evidence suggests that lack of TGF-¦Â1 signalling promotes the development of atherosclerotic lesions and unstable plaques [10]. Therefore, because impairment in the TGF-¦Â1 pathway has been associated with both an SLE-like illness and enhanced atherogenesis, we hypothesize that this pathway might represent a link between th
%U http://arthritis-research.com/content/8/3/R81