Immunomodulatory properties of increased levels of liver X receptor beta in peripheral blood mononuclear cells from multiple sclerosis patients.
Exp Neurol. 2007 Jan 24; [Epub ahead of print]
Giorelli M, Livrea P, Minervini MG, Trojano M.
Department of Neurologic and Psychiatric Sciences, University of Bari, Bari, Italy; U.O. of Neurology, "Casa della Divina Provvidenza", Bisceglie (Bari), Italy; Laboratory of Neurogenetics and Experimental Neurobiology, "Casa della Divina Provvidenza", Bisceglie (Bari), Italy.
Liver X receptors (LXRalpha and LXRbeta) are nuclear transcription factors that inhibit transcription of genes of inflammation while inducing HMGCoA reductase. In this paper we demonstrate increased mRNA levels of LXRbeta in peripheral blood mononuclear cells (PBMCs) from multiple sclerosis patients with respect to other neurological patients and healthy controls (HC) (p<0.01). Agonist-induced activation of LXRs partially counteracts the anti-CD3+ anti-CD28-induced proliferation of T cells (p<0.01) and secretion of IFNgamma (p<0.001) from PBMCs of MS patients as well as of HC. Secretion of IL-4 is not affected. Our findings suggest that regulation of cholesterol metabolism not strictly related to inhibition of HMGCoA reductase can modulate activity of lymphocytes in MS.
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