Prevention of collagen-induced arthritis in DBA/1 mice by oral administration of AZ-9, a bacterial polysaccharide from Klebsiella oxytoca.
Collagen-induced arthritis (CIA) is an excellent model of rheumatoid arthritis (RA) in humans that is induced in DBA/1 mice immunized with bovine type II collagen (CII). Here, we report that the induction of CIA was effectively suppressed by oral administration of AZ-9, a purified polysaccharide with the average molecular weight of approximately 200 kDa that was produced by a soil bacterium, Klebsiella oxytoca. When AZ-9 was administered at 125-250 mg/kg/day orally for 9 consecutive days after immunization with CII followed by its administration every 3 days, resulted in a marked reduction of the incidence and the severity of CIA. The serum level of anti-CII IgG2a and the production of IFN-gamma and IL-12 in the draining lymph node (LN) cells were significantly lower in AZ-9-administered mice than the untreated control. These findings suggest that orally administered AZ-9 suppressed CIA through attenuating a Th1-type response to CII. AZ-9 could be fragmented into smaller molecules (3-4 kDa) without losing its suppressive activity.
Sugihara
R
R
Department of Biotechnology, Faculty of Engineering, Okayama University, Tsushima-Naka, 700 8530, Okayama, Japan.
Yoshimura
M
M
Mori
M
M
Kanayama
N
N
Hikida
M
M
Ohmori
H
H
D000284:Administration, Oral; D000818:Animals; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001168:Arthritis / Q000473:pathology / Q000517:prevention & control*; D002240:Carbohydrate Sequence; D002417:Cattle; D003094:Collagen / Q000276:immunology*; D007074:Immunoglobulin G / Q000096:biosynthesis; D007709:Klebsiella / Q000737:chemistry* / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D011135:Polysaccharides, Bacterial / Q000008:administration & dosage*; D020449:Repetitive Sequences, Amino Acid
D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D011135:Polysaccharides, Bacterial; D003094:Collagen