Salmon proteoglycan suppresses progression of mouse experimental autoimmune encephalomyelitis via regulation of Th17 and Foxp3(+) regulatory T cells.
OBJECTIVE
Proteoglycans (PGs) are complex glycohydrates, which are composed of core proteins and glycosaminoglycans and widely distributed in connective tissues. We investigated the effect of PG extracted from salmon cartilage in progression of mouse experimental autoimmune encephalomyelitis (EAE).


METHODS
EAE was induced by immunization with myelin-oligodendrocyte glycoprotein (MOG). Mice were given orally once daily with salmon cartilage PG and severity of EAE was monitored. Expression of Th17- and regulatory T cell-related factors was determined by ELISA and/or quantitative real time PCR. Expression of Foxp3(+) in CD4(+)CD25(+) cells was analyzed by flow cytometry.


RESULTS
Daily oral administration of PG attenuated clinical and histological severity of EAE in a dose-dependent manner. It suppressed interferon-β (IFN-β) production and CCL2 expression in spinal cord that is the inflamed site of EAE. Administration of PG suppressed IFN-γ and interleukin-17 (IL-17) production from lymphocytes from draining lymph nodes in response to MOG re-stimulation ex vivo. Moreover, administration of PG suppressed the expression of IL-6, IL-21, IL-23 receptor and retinoic acid-related orphan receptor γt and enhanced the expression of Foxp3 in both draining lymph nodes and spinal cords.


CONCLUSIONS
Salmon cartilage PG attenuates the severity of EAE by suppressing the differentiation of Th17 linage and enhancement of Treg expansion. Our results indicated that PG has potential to be a novel prophylactic agent for autoimmune diseases.
Department of Microbiology and Immunology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, 036-8562, Japan.
Hiroshi
H
Sashinami
Krisana
K
Asano
Sayuri
S
Yoshimura
Fumiaki
F
Mori
Koichi
K
Wakabayashi
Akio
A
Nakane
D000284:Administration, Oral; D000818:Animals; D002356:Cartilage / Q000737:chemistry; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology*; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D011509:Proteoglycans / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D012474:Salmon; D012720:Severity of Illness Index; D013116:Spinal Cord / Q000187:drug effects / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D011509:Proteoglycans