Effect of the C3a-receptor antagonist SB 290157 on anti-OVA polyclonal antibody-induced arthritis.
It was investigated whether the C3a-receptor antagonist (C3aRA) SB 290157 was involved in the suppression of anti-OVA pAb-induced arthritis because it is well known that anaphylatoxin C3a plays a crucial role in the development of an effective inflammatory response during complement activation. Anti-OVA pAb-induced arthritis was induced in DBA/1J mice by administration of anti-OVA pAb 0.5 h prior to intra-articular (i.a.) injection of OVA (0 h). Two peaks of joint swelling were observed at 0.5 and 3 h. The role of C3aRA in arthritis was investigated by injection of SB 290157 at concentrations of 10 and 30 mg/kg at 0 and 2 h. The antagonist was able to reduce joint swelling only at 3 h, and about 50% inhibition of joint swelling was observed with the concentration of 30 mg/kg. The C3 level was significantly decreased at 3 h compared with naïve mice showing complement consumption. Furthermore, the C3 activation was observed and increased corresponding to the graded concentration of anti-OVA pAb. The results also revealed that the C3aRA was able to reduce the expression of IL-1beta in synovial tissue. Taken together, the results suggested that C3aRA may be effective in the inhibition of arthritis.
Hutamekalin
Pilaiwanwadee
P
Department of Pharmacology, Kobe Pharmaceutical University, Japan.
Takeda
Kohei
K
Tani
Mitsuhiro
M
Tsuga
Yuko
Y
Ogawa
Naoki
N
Mizutani
Nobuaki
N
Yoshino
Shin
S
D000818:Animals; D000906:Antibodies / Q000633:toxicity*; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D001559:Benzhydryl Compounds / Q000494:pharmacology* / Q000627:therapeutic use*; D015926:Complement C3a / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D010063:Ovum / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D011951:Receptors, Complement / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism
D000906:Antibodies; D001559:Benzhydryl Compounds; D011951:Receptors, Complement; C431907:SB 290157; D015926:Complement C3a; D001120:Arginine