Immunomodulatory properties of increased levels of liver X receptor beta in peripheral blood mononuclear cells from multiple sclerosis patients.
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.
Giorelli
Maurizio
M
Department of Neurologic and Psychiatric Sciences, University of Bari, and Casa della Divina Provvidenza, Via Bovio 84, Bisceglie, Bari, Italy. mgiorelli@libero.it
Livrea
Paolo
P
Minervini
Mauro Giuseppe
MG
Trojano
Maria
M
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D015703:Antigens, CD / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000819:agonists / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D006845:Hydrocarbons, Fluorinated; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism*; D000071518:Liver X Receptors; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology*; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D018709:Statistics, Nonparametric; D013449:Sulfonamides / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D015703:Antigens, CD; D004268:DNA-Binding Proteins; D006845:Hydrocarbons, Fluorinated; D006903:Hydroxymethylglutaryl CoA Reductases; D007371:Interferon-gamma; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D013449:Sulfonamides; C000605213:NR1H3 protein, human; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides