Abstract |
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.
|
Authors | Pilaiwanwadee Hutamekalin, Kohei Takeda, Mitsuhiro Tani, Yuko Tsuga, Naoki Ogawa, Nobuaki Mizutani, Shin Yoshino |
Journal | Journal of pharmacological sciences
(J Pharmacol Sci)
Vol. 112
Issue 1
Pg. 56-63
( 2010)
ISSN: 1347-8648 [Electronic] Japan |
PMID | 20051658
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Antibodies
- Benzhydryl Compounds
- Receptors, Complement
- SB 290157
- Complement C3a
- Arginine
|
Topics |
- Animals
- Antibodies
(toxicity)
- Arginine
(analogs & derivatives, pharmacology, therapeutic use)
- Arthritis, Experimental
(immunology, metabolism, prevention & control)
- Benzhydryl Compounds
(pharmacology, therapeutic use)
- Complement C3a
(antagonists & inhibitors, metabolism)
- Male
- Mice
- Mice, Inbred DBA
- Ovum
(immunology)
- Rats
- Rats, Inbred Lew
- Receptors, Complement
(antagonists & inhibitors, immunology, metabolism)
|