The HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease

Nature

Volumn 420, Issue 6911, 2002, Pages 78-84

  Youssef, Sawsan ^a   Stüve, Olaf ^c   Patarroyo, Juan O ^c   Ruiz, Pedro J ^a,d   Radosevich, Jennifer L ^a   Mi Hur, Eun ^a   Bravo, Manuel ^c   Mitchell, Dennis J ^a   Sobel, Raymond A ^b   Stelnman, Lawrence ^a   Zamvil, Scott S ^c  

^a Beckman Center for Molecular Medicine   (United States)

^b STANFORD UNIVERSITY   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d CALIFORNIA PACIFIC MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIGENS; COENZYMES; ENZYME INHIBITION; IMMUNOLOGY; REDUCTION; TUMORS;

PHOSPHORYLATIONS;

NEUROLOGY;

ATORVASTATIN; B7 ANTIGEN; CD4 ANTIGEN; CD40 ANTIGEN; CD86 ANTIGEN; CYTOKINE; GAMMA INTERFERON; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; INTERLEUKIN 10; INTERLEUKIN 12; INTERLEUKIN 2; INTERLEUKIN 4; INTERLEUKIN 5; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 2; MEVALONIC ACID; STAT4 PROTEIN; STAT6 PROTEIN; STATIN; TRANSFORMING GROWTH FACTOR BETA; TUMOR NECROSIS FACTOR ALPHA;

BIOCHEMISTRY; NERVOUS SYSTEM DISORDER;

ALLERGIC ENCEPHALOMYELITIS; ANIMAL CELL; ANIMAL MODEL; ANTIGEN PRESENTING CELL; ARTICLE; AUTOIMMUNE DISEASE; CELL DIFFERENTIATION; CENTRAL NERVOUS SYSTEM; CONTROLLED STUDY; DEMYELINATING DISEASE; DISEASE MODEL; FEMALE; IMMUNOMODULATION; INFLAMMATORY DISEASE; LYMPHOCYTE ACTIVATION; MICROGLIA; MOUSE; MULTIPLE SCLEROSIS; NONHUMAN; PARALYSIS; PRIORITY JOURNAL; T LYMPHOCYTE; TH1 CELL; TH2 CELL;

ADOPTIVE TRANSFER; AMINO ACID SEQUENCE; ANIMALS; ANTIGEN-PRESENTING CELLS; CELL DIVISION; CENTRAL NERVOUS SYSTEM DISEASES; CYTOKINES; DNA-BINDING PROTEINS; ENCEPHALOMYELITIS, AUTOIMMUNE, EXPERIMENTAL; FEMALE; GENE EXPRESSION; HEPTANOIC ACIDS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; MACROPHAGES; MICE; MICROGLIA; MOLECULAR SEQUENCE DATA; MULTIPLE SCLEROSIS; NUCLEAR PROTEINS; PARALYSIS; PHOSPHORYLATION; PYRROLES; RNA, MESSENGER; STAT4 TRANSCRIPTION FACTOR; STAT6 TRANSCRIPTION FACTOR; TH2 CELLS; TRANS-ACTIVATORS;

ANIMALIA;

EID: 0037038402     PISSN: 00280836     EISSN: None     Source Type: Journal    
DOI: 10.1038/nature01158     Document Type: Article

References (30)

1. Kobashigawa, J. A. et al. Effect of pravastatin on outcomes after cardiac transplantation. N. Engl. J Med. 333, 621-627 (1995).
2. Pahan, K., Sheikh, F. G., Namboodiri, A. M. & Singh, I. Lovastatin and phenylacetate inhibit the induction of nitric oxide synthase and cytokines in rat primary astrocytes, microglia, and macrophages. J. Clin. Invest. 100, 2671-2679 (1997).
3. Wong, B. et al. Statins suppress THP-1 cell migration and secretion of matrix metalloproteinase 9 by inhibiting geranylgeranylation. J Leukoc. Biol. 69, 959-962 (2001).
4. Zamvil, S. S. & Steinman, L. The T lymphocyte in experimental allergic encephalomyelitis. Annu. Rev. Immunol. 8, 579-621 (1990).
5. Slavin, A. J. et al. Requirement for endocytic antigen processing and influence of invariant chain and H-2M deficiencies in CNS autoimmunity. J. Clin. Invest. 108, 1133-1139 (2001).
6. Romano, M. et al. Inhibition of monocyte chemotactic protein-1 synthesis by statins. Lab. Invest. 80, 1095-1100 (2000).
7. Steinman, L., Rosenbaum, J. T., Sriram, S. & McDevitt, H. O. In vivo effects of antbodies to immune response gene products; prevention of experimental allergic encephalomyelitis. Proc. Natl Acad. Sci. USA 78, 7111-7114 (1981).
8. Bottazo, G. E., Pujol-Borrell, R., Hanufusa, T. & Feldmann, M. Role of aberrant HLA-DR expression and antigen presentation in induction of endocrine autoimmunity. Lancet 2, 1115-1119 (1983).
9. Kwak, B., Mulhaupt, F., Myit, S. & Mach, F. Statins as a newly recognized type of immunomodulator. Nature Med. 6, 1399-1402 (2000).
10. Mach, B., Steimle, V., Martinez-Soria, E. & Reith, W, Regulation of MHC class II genes: Lessons from a disease. Annu. Rev. Immunol. 14, 301-331 (1996).
11. Muhlethaler-Mottet, A., Otten, L. A., Steinle, V. & Mach, B. Expression of MHC class II molecules in different cellular and functional compartments is controlled by differential usage of multiple promoters of the transactivator CIITA. EMBO J. 16, 2851-2860 (1997).
12. Maeda, A. & Sobel, R. A. Matrix metalloproteinases in the normal human central nervous system, microglial nodules, and multiple sclerosis lesions. J. Neuropathol. Exp. Neurol. 55, 300-309 (1996).
13. Rudick, R. A. Contemporary immunomodulatory therapy for multiple sclerosis. J. Neuroophthalmol. 21, 284-291 (2001).
14. Staffa, J. A., Chang, J. & Green, L. Cerivastatin and reports of fatal rhabdomyolysis. N. Engl. Med. 346, 539-540 (2002).
15. Bernini, F., Poli, A. & Paoletti, R. Safety of HMG-CoA reductase inhibitors: Focus on alorvastatin. Cardiovasc. Drugs Ther: 15, 211-218 (2001).
16. Cilla, D. D. Jr, Whitfield, L. R., Gibson, D. M., Sedman A. J. & Posvar, E. L. Multiple-dose pharmacokioetics, pharmacodynamics, and safety and atorvastatin, an inhibitor of HMG-CoA reductase, in healthy subjects. Clin. Pharmacol. Ther. 60, 687-695 (1996).
17. Dostal, L. A., Whitfield, I. R. & Anderson, J. A. Fertility and general reproduction studies in rats with the HMG-CoA reductase inhibitor, atorvastatin. Fundam. Appl. Toxicol. 32, 285-292 (1996).
18. Hardardotlir, E, Baron, J. L. & Janeway, C. A. Jr. T cells with two functional antigen-specific receptors. Proc. Natl Acad. Sci. USA 92, 354-358 (1995).
19. Piskurich, J. F., Linhoff, M. W., Wang, Y. & Ting, J. P. Y. Two distinct gamma interferon-inducible promoters of the major histocompatibilily complex class II transactivator gene are differentially regulated by STAT1, interferon regulatory factor 1, and transforming growth factor beta. Mol. Cell Biol. 19, 431-440 (1999).
20. Waldburger, J. M., Suter, T., Fontana, A., Acha-Orbea, H. & Reith, W. Selective abrogation of major histocompatibility complex class II expression on extrahematopoietic cells in mice lacking promoter IV of the class II transactivator gene. J. Exp. Med. 194, 393-406 (2001).
21. + T-cell activation. Glia 36, 391-405 (2001).
22. Darnell, J. E. Jr. STATs and gene regulation. Science 277, 1630-1635 (1997).
23. Weitz-Schmidt, G. et al. Statins selectively inhibit leukocyte fundion antigen-1 by binding to a novel regulatory integrin site. Nature Med. 7, 687-692 (2001).
24. Goldstein, J. L. & Brown, M. S. Regulation of the mevalonate pathway. Nature 343, 425-430 (1990).
25. Cuthbert, J. A. & Lipsky, P. E. Sterol metabolism and lymphocyte responsiveness: Inhibition of endogenous sterol synthesis prevents mitogen-induced human T cell proliferation. Immunol. 126, 2093-2099 (1981).
26. Steinman, L. Multiple sclerosis: A two-stage disease. Nature Immunol. 2, 762-764 (2001).
27. Stanislaus, R., Pahan, K., Singh, A. K. & Singh, I. Amelioration of experimental allergic encephalomyelitis in Lewis rats by lovastatin. Neurosci. Lett. 269, 71-74 (1999).
28. + T cells. J. Neuroimmunol. 63, 163-174 (1995).
29. + T cell priming and Th1/Th2 cell restimulation. Eur. J. Immunol. 29, 2705-2714 (1999).
30. Soos, J. M. et al. Astrocytes express elements of the class II endocytic pathway and process central nervous system autoantigen for presentation for encephalitogenic T cells. J. Immunol. 161, 5959-5966 (1998).