Bowman-Birk inhibitor suppresses autoimmune inflammation and neuronal loss in a mouse model of multiple sclerosis.
The Bowman-Birk inhibitor (BBI) is a soybean-derived serine protease inhibitor. BBI concentrate (BBIC) is an extract enriched with BBI, but predominantly contains other ingredients including several protease inhibitors. We previously found that BBIC administration to Lewis rats with experimental autoimmune encephalomyelitis (EAE) significantly suppresses disease. In the present study we determined whether BBI mediates the suppressive effects of BBIC in EAE, evaluated its potential neuroprotective effects, and investigated mechanisms of BBI action. We tested effects of purified BBI on clinical and histopathological parameters of EAE in two models (relapsing/remitting EAE in SJL/J mice and chronic EAE in C57BL/6 mice). Effects of BBI were compared to BBIC in relapsing/remitting EAE, and effects of BBI on neuronal survival were examined during acute optic neuritis. Treatment with BBI in both EAE models significantly improved EAE disease parameters (onset, severity, weight loss, inflammation and demyelination). BBI significantly reduced the incidence of optic neuritis and prevented loss of retinal ganglion cells. In most experiments proliferation of immune cells derived from BBI-treated mice was significantly lower relative to control groups. Using Boyden's chamber assay we found that BBI inhibited invasiveness of activated splenocytes through the matrigel barrier. BBI also induced higher production of EAE-suppressive cytokine IL-10 by immune cells. These results demonstrate that BBI is the active component of BBIC that ameliorates clinical EAE. BBI reduces inflammation and attenuates neuronal loss, making it an excellent candidate for oral therapy in MS. BBI likely ameliorates EAE by inhibiting multiple pathways involved in disease pathogenesis.
Touil
Tarik
T
Department of Neurology, Thomas Jefferson University, Jefferson Hospital for Neuroscience, 900 Walnut Street, Suite 300, Philadelphia, PA 19107, USA.
Ciric
Bogoljub
B
Ventura
Elvira
E
Shindler
Kenneth S
KS
Gran
Bruno
B
Rostami
Abdolmohamad
A
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002490:Central Nervous System / Q000166:cytology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009103:Multiple Sclerosis / Q000188:drug therapy; D018991:Myelin Proteolipid Protein / Q000235:genetics; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000235:genetics; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000187:drug effects; D014358:Trypsin Inhibitor, Bowman-Birk Soybean / Q000627:therapeutic use*
D016207:Cytokines; D018991:Myelin Proteolipid Protein; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D014358:Trypsin Inhibitor, Bowman-Birk Soybean; C435023:myelin proteolipid protein (139-151)