Amelioration of experimental autoimmune encephalitis by novel peptides: involvement of T regulatory cells.
The purpose of the present study was to develop a peptide for treatment of multiple sclerosis (MS). We have tested the effect of a novel anti-inflammatory peptide (KGHYAERVG, termed IIIM1) on experimental autoimmune encephalitis (EAE), an animal model of MS. Our findings demonstrate significant reduction in neurological score following oral administration of IIIM1. Structural studies revealed that the entire peptide is required for activity. The peptide caused significant reduction in IL17, interferon gamma, IL23 and IL12 production by isolated splenocytes and concomitant elevation of anti-inflammatory cytokines. IIIM1 elevated T regulatory cells (Tregs, CD4(+)CD25(+)FoxP3(+)) in brain and spleen of EAE mice. Similar proliferative effect was observed in isolated human and mouse Tregs in vitro. Stimulation of Tregs by IIIM1 caused production of a new peptide termed RA1 present in Oryza Sativa Japonica group. This Japanese rice peptide ameliorated neurological symptoms in the EAE model. Similar beneficial effect was observed upon oral administration of an extract of Japanese rice. In conclusion, oral treatment with IIIM1 ameliorates EAE symptoms via stimulation of Tregs to proliferate and produce RA1 which reduces EAE symptoms. RA1 might be involved in the relatively low prevalence of MS in Japan and other Japanese rice-eating populations.
Shapira
Elena
E
Institute of Drug Research, School of Pharmacy, Faculty of Medicine, Institute of Life Sciences, The Hebrew University, POB 12065, 91120 Jerusalem, Israel.
Brodsky
Berta
B
Proscura
Elena
E
Nyska
Abraham
A
Erlanger-Rosengarten
Avigail
A
Wormser
Uri
U
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D015704:CD4 Antigens / Q000096:biosynthesis; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D005620:Freund's Adjuvant; D006023:Glycoproteins / Q000008:administration & dosage; D006657:Histones / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology; D018991:Myelin Proteolipid Protein / Q000008:administration & dosage; D063308:Myelin-Oligodendrocyte Glycoprotein; D012275:Oryza; D010446:Peptide Fragments / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D010936:Plant Extracts; D010940:Plant Proteins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D000893:Anti-Inflammatory Agents; D015704:CD4 Antigens; D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D006023:Glycoproteins; D006657:Histones; D053645:Interleukin-2 Receptor alpha Subunit; D018991:Myelin Proteolipid Protein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D010936:Plant Extracts; D010940:Plant Proteins; C445081:myelin oligodendrocyte glycoprotein (35-55); C435023:myelin proteolipid protein (139-151); D005620:Freund's Adjuvant