Effects of IFN-B on TRAIL and Decoy Receptor Expression in Different Immune Cell Populations from MS Patients with Distinct Disease Subtypes.
Using quantitative RT-PCR, we compared mRNA levels for TRAIL [tumor necrosis factor (TNF)-related apoptosis-inducing ligand] and its receptors in various immune cell subsets derived from the peripheral blood of untreated normal subjects (NS) and patients with distinct subtypes of multiple sclerosis (MS): active relapsing-remitting MS (RRA), quiescent relapsing-remitting MS (RRQ), secondary-progressive MS (SPMS) or primary-progressive MS (PPMS). Consistent with a role for TRAIL in the mechanism of action of interferon-β (IFN-β), TRAIL mRNA levels were increased in monocytes from patients clinically responsive to IFN-β (RRQ) but not those unresponsive to this therapeutic (RRA). TRAIL-R3 (decoy receptor) expression was elevated in T cells from untreated RRMS patients while IFN-β therapy reversed this increase suggesting that IFN-β may promote the apoptotic elimination of autoreactive T cells by increasing the amount of TRAIL available to activate TRAIL death receptors. Serum concentrations of soluble TRAIL were increased to a similar extent by IFN-β therapy in RRQ, RRA and SPMS patients that had not generated neutralizing antibodies against this cytokine. Although our findings suggest altered TRAIL signaling may play a role in MS pathogenesis and IFN-β therapy, they do not support use of TRAIL as a surrogate marker for clinical responsiveness to this therapeutic.
Department of Pharmacology, Dalhousie University, Halifax, NS, Canada B3H 1X5.
Andrea L O
AL
Hebb
Craig S
CS
Moore
Virender
V
Bhan
George S
GS
Robertson
Neuron. 2005 May 5;46(3):421-32
15882642
Trends Pharmacol Sci. 2003 Mar;24(3):131-8
12628358
Recent Prog Horm Res. 1999;54:225-34
10548878
J Clin Immunol. 2004 Jan;24(1):1-11
14997028
Science. 1983 Jan 21;219(4582):308-10
6217550
J Neuroimmunol. 2007 Oct;190(1-2):170-6
17884184
Cell Death Differ. 2000 Jul;7(7):637-44
10889508
J Neuroimmunol. 2007 Mar;184(1-2):17-26
17222462
Curr Dir Autoimmun. 2006;9:1-17
16394652
Clin Neurol Neurosurg. 2010 Jun;112(5):365-85
20362388
J Infect Dis. 2005 Feb 15;191(4):571-8
15655781
Clin Neurosci. 1994;2(3-4):229-45
7749893
J Neurol Neurosurg Psychiatry. 2003 Jun;74(6):695-7
12754330
Acta Neurol Scand. 2001 Nov;104(5):249-56
11696016
Curr Med Res Opin. 2007 Nov;23(11):2823-32
17908370
Mult Scler. 2005 Dec;11(6):652-7
16320724
Neurology. 2002 Sep 24;59(6):802-8
12349849
Neurology. 2010 Jan 5;74 Suppl 1:S17-24
20038758
Int Rev Neurobiol. 2007;79:99-126
17531839
BMC Cancer. 2005 May 25;5:54
15916713
N Engl J Med. 2008 Feb 14;358(7):676-88
18272891
Curr Opin Neurol. 2003 Jun;16(3):267-73
12858061
Mol Cell Biol. 2006 Oct;26(19):7046-55
16980609
Immunol Cell Biol. 2005 Oct;83(5):511-9
16174101
Lancet. 2003 Jun 14;361(9374):2036-43
12814715
J Mol Med (Berl). 1997 Mar;75(3):165-73
9106073
Mult Scler. 2008 Jun;14(5):577-94
18566024
Neuroscientist. 2006 Aug;12(4):305-16
16840707
Methods. 2001 Dec;25(4):402-8
11846609
Front Biosci. 2007 May 01;12:2912-21
17485268
Nat Med. 1999 Feb;5(2):153-4
9930860
Immunol Rev. 1999 Jun;169:81-92
10450510
N Engl J Med. 2000 Sep 28;343(13):938-52
11006371
Neurobiol Dis. 2005 Apr;18(3):537-50
15755681
Cancer Gene Ther. 2004 Oct;11(10):681-90
15332116