LY309887, antifolate via the folate receptor suppresses murine type II collagen-induced arthritis.
OBJECTIVE
To examine the effect of LY309887, an inhibitor of glycinamide ribonucleotide formyltransferase in de novo purine biosynthesis on murine type collagen-induced arthritis (CIA).


METHODS
CIA was induced by immunization with bovine type II collagen in adjuvant. The expression of folate receptors was examined in dissected synovial tissues and bone marrow cells from arthritic and non-arthritic mice by the semi-quantitative reverse transcription-polymerase chain reaction. LY309887 was administered to CIA mice after the onset of arthritis. Mice were monitored for arthritis index for 21 days. Levels of IgG1 and IgG2a antibodies against bovine type II collagen were measured in sera from CIA mice with or without LY309887 treatment by the enzyme-linked immunosorbent assay. Histologic analyse were also performed in synovial tissues from arthritic joints with or without LY309887 treatment.


RESULTS
Levels of mRNA of folate receptor beta (FR-beta) were elevated in arthritic joints from CIA mice, compared with those in nonarthritic joints. The expression of mRNA of FR-beta was dominant in bone marrow cells of CIA mice. The administration of LY309887 suppressed the disease progression of CIA mice as defined by the lower arthritis index, and decreased production of serum IgG1 and IgG2a anti-type II collagen antibody, and the damage to cartilage or bone.


CONCLUSIONS
The administration of LY309887 was effective on CIA mice. It was suggested that LY309887 might be useful in the treatment of rheumatoid arthritis.
Nagayoshi
R
R
Department of Orthopaedic Surgery, School of Medicine, Kagoshima University, Sakuragaoka, Kagoshima City, Japan.
Nakamura
M
M
Ijiri
K
K
Yoshida
H
H
Komiya
S
S
Matsuyama
T
T
D000818:Animals; D001168:Arthritis / Q000188:drug therapy* / Q000473:pathology*; D001483:Base Sequence; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism*; D024043:Collagen Type II; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D058973:Folate Receptors, GPI-Anchored; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011336:Probability; D011897:Random Allocation; D011956:Receptors, Cell Surface; D018570:Risk Assessment; D018709:Statistics, Nonparametric; D013583:Synovial Membrane / Q000187:drug effects / Q000473:pathology; D013763:Tetrahydrofolates / Q000494:pharmacology*
C105065:6R-2',5'-thienyl-5,10-dideazatetrahydrofolic acid; D002352:Carrier Proteins; D024043:Collagen Type II; D058973:Folate Receptors, GPI-Anchored; D011956:Receptors, Cell Surface; D013763:Tetrahydrofolates