Dipeptidyl peptidase IV in inflammatory CNS disease.
Current pathogenic concepts of inflammatory demyelinating disorders such as multiple sclerosis (MS) are based on the hypothesis that a T cell-mediated autoimmune response is involved in the disease process. One of the primary goals in the in the development of immunotherapies for autoimmune diseases has been to achieve inactivation of disease-inducing lymphocytes either by direct inhibition or suppression through regulatory cells and/or cytokines. The CD26 antigen is identical with the cell surface ectopeptidase dipeptidyl peptidase IV (DP IV, EC 3.4.14.5) which is involved in regulating T cell activation and growth. Activated T cells, including those specific for myelin antigens, express high levels of CD26/DP IV. In vitro, reversible DP IV inhibitors suppress T cell proliferation and pro-inflammatory cytokine production in response to myelin antigens. Further studies will evaluate the role of DP IV inhibition in T cell-mediated inflammatory disease of the central nervous system.
Steinbrecher
A
A
National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Reinhold
D
D
Quigley
L
L
Gado
A
A
Tresser
N
N
Izikson
L
L
Born
I
I
Faust
J
J
Neubert
K
K
Martin
R
R
Ansorge
S
S
Brocke
S
S
D000818:Animals; D021461:Animals, Outbred Strains; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000201:enzymology*; D018819:Dipeptidyl Peptidase 4 / Q000187:drug effects / Q000502:physiology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000201:enzymology*; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D008239:Lysine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D009103:Multiple Sclerosis / Q000201:enzymology*; D004676:Myelin Basic Protein / Q000276:immunology*; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000201:enzymology / Q000276:immunology; D013844:Thiazoles / Q000494:pharmacology*
D004676:Myelin Basic Protein; D011759:Pyrrolidines; D015842:Serine Proteinase Inhibitors; D013844:Thiazoles; C110164:lysyl-(Z(nitro))pyrrolidide; C093632:lysyl-(Z(nitro))thiazolidide; D018819:Dipeptidyl Peptidase 4; D008239:Lysine