title: Bowman-Birk Inhibitor attenuates experimental autoimmune encephalomyelitis by delaying infiltration of inflammatory cells into the CNS.
abstract: Bowman-Birk Inhibitor (BBI), a serine protease inhibitor derived from soybeans, has anti-inflammatory properties and is able to suppress the development of central nervous system (CNS) autoimmunity in animal models. Experimental autoimmune encephalomyelitis (EAE), a widely used animal model of multiple sclerosis (MS), is characterized by breakdown of the blood-brain barrier and infiltration of inflammatory cells into the CNS, resulting in pathology. In this study, we observed that BBI-treated mice showed delayed onset of EAE and reduced disease severity compared to control mice. BBI-treated mice had fewer inflammatory cells in the CNS including significantly reduced numbers of Th1 and Th17 cells. In the periphery, BBI treatment suppressed the development of encephalitogenic Th1 and Th17 responses early on [day 7 post-immunization (p.i.)], while after disease onset (day 14 p.i.) BBI-treated mice had stronger Th responses, as determined by antigen-specific proliferation and cytokine production. These results demonstrate that BBI treatment temporarily suppressed the development of encephalitogenic responses, but these responses eventually attained normal magnitude. Given that BBI-treated mice exhibited stronger encephalitogenic responses in the periphery during clinically manifesting EAE, delayed disease onset, and reduced numbers of CNS-infiltrating cells, it appears likely that BBI impedes the exit of pathogenic Th1 and Th17 cells from lymphoid organs, thereby delaying their migration into the CNS.
authors.affiliation: Department of Neurology, Thomas Jefferson University, Jefferson Hospital for Neuroscience, 900 Walnut Street, Suite 300, Philadelphia, PA 19107, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Dai
authors.forename: Bogoljub
authors.initials: B
authors.lastname: Ciric
authors.forename: Guang-Xian
authors.initials: GX
authors.lastname: Zhang
authors.forename: Abdolmohamad
authors.initials: A
authors.lastname: Rostami
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002490:Central Nervous System / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology; D014358:Trypsin Inhibitor, Bowman-Birk Soybean / Q000008:administration & dosage*
chemical_list: D016207:Cytokines; D014358:Trypsin Inhibitor, Bowman-Birk Soybean
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