The differential effect of high and low molecular weight fucoidans on the severity of collagen-induced arthritis in mice.
Fucoidans have been extensively studied for their various biological activities but the exact role of fucoidans on the inflammatory processes associated with arthritic disease has not been studied. The effect of the treatment of high, medium and low molecular weight fucoidans (HMWF, MMWF and LMWF, respectively) on the progression of collagen-induced arthritis (CIA) was tested. A daily oral administration of HMWF enhanced the severity of arthritis, inflammatory responses in the joint cartilage and the levels of collagen-specific antibodies, while LMWF reduced the severity of arthritis and the levels of Th1-dependent collagen-specific IgG(2a). Further in vitro analyses, using macrophage cell lines, revealed that the HMWF induced the expression of various inflammatory mediators, and enhanced the cellular migration of macrophages. These stimulatory effects of fucoidan decreased in fucoidans with lower molecular weights and LMWF did not exhibit any pro-inflammatory effects. Interestingly, the oral administration of HMWF enhanced the production of IFN-gamma, one of the Th1 cytokines, in collagen-stimulated spleen cells that had been isolated from CIA mice, while LMWF had the opposite effect. These results indicate that HMWF enhances arthritis through enhancing the inflammatory activation of macrophages while LMWF reduces arthritis through the suppression of Th1-mediated Immune reactions.
Park
Seung-Beom
SB
Department of Genetic Engineering, School of Life Sciences and Biotechnology, Kyungpook National University, Daegu 702-701, Korea.
Chun
Kwang-Rok
KR
Kim
Jae-Kwan
JK
Suk
Kyungho
K
Jung
Young-Mi
YM
Lee
Won-Ha
WH
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D002356:Cartilage / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D024043:Collagen Type II; D007074:Immunoglobulin G / Q000097:blood; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis; D007596:Joints / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008970:Molecular Weight; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D011134:Polysaccharides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D012720:Severity of Illness Index; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D018417:Th1 Cells / Q000378:metabolism; D044648:Undaria / Q000737:chemistry*
D000893:Anti-Inflammatory Agents; D024043:Collagen Type II; D007074:Immunoglobulin G; D018836:Inflammation Mediators; D010936:Plant Extracts; D011134:Polysaccharides; D007371:Interferon-gamma; C007789:fucoidan