Abstract
The angiotensin II type 1 receptor (AT1R) blocker losartan ameliorates rheumatoid arthritis (RA) in an experimental model. In RA, AT2R mainly opposes AT1R, but the mechanism by which this occurs still remains obscure. In the present study, we investigated the role of AT2R in the treatment of rats with adjuvant-induced arthritis (AIA) by losartan. Adjuvant-induced arthritis rats were treated with losartan (5, 10 and 15 mg/kg) and methotrexate (MTX; 0.5 mg/kg) in vivo from day 14 to day 28. Arthritis was evaluated by the arthritis index and histological examination. Angiotensin II, tumour necrosis factor-α, and VEGF levels were examined by ELISA. The expression of AT1R and AT2R was detected by western blot and immunohistochemistry analysis. After stimulation with interleukin-1β in vitro, the effects of the AT2R agonist CGP42112 (10-8-10-5 M) on the chemotaxis of monocytes induced by 10% foetal calf serum (FCS) were analysed by using Transwell assay. Subsequently, the therapeutic effects of CGP42112 (5, 10 and 20 μg/kg) were evaluated in vivo by intra-articular injection in AIA rats. After treatment with losartan, the down-regulation of AT1R expression and up-regulation of AT2R expression in the spleen and synovium of AIA rats correlated positively with reduction in the polyarthritis index. Treatment with CGP42112 inhibited the chemotaxis of AIA monocytes in vitro, possibly because of the up-regulation of AT2R expression. Intra-articular injection with CGP42112 (10 and 20 μg/kg) ameliorated the arthritis index and histological signs of arthritis. In summary, the present study strongly suggests that the up-regulation of AT2R might be an additional mechanism by which losartan exerts its therapeutic effects in AIA rats.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1577-1587 |
| Number of pages | 11 |
| Journal | Journal of Cellular and Molecular Medicine |
| Volume | 17 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 1 2013 |
| Externally published | Yes |
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Keywords
- Adjuvant-induced arthritis
- Angiotensin II type 2 receptor
- Losartan
- Rheumatoid arthritis
ASJC Scopus subject areas
- Molecular Medicine
- Cell Biology
Cite this
Angiotensin II type 2 receptor correlates with therapeutic effects of losartan in rats with adjuvant-induced arthritis. / Wang, Di; Hu, Shanshan; Zhu, Jie; Yuan, Jun; Wu, Jingjing; Zhou, Aiwu; Wu, Yujing; Zhao, Wendi; Huang, Qiong; Chang, Yan; Wang, Qingtong; Sun, Wuyi; Wei, Wei.
In: Journal of Cellular and Molecular Medicine, Vol. 17, No. 12, 01.12.2013, p. 1577-1587.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Angiotensin II type 2 receptor correlates with therapeutic effects of losartan in rats with adjuvant-induced arthritis
AU - Wang, Di
AU - Hu, Shanshan
AU - Zhu, Jie
AU - Yuan, Jun
AU - Wu, Jingjing
AU - Zhou, Aiwu
AU - Wu, Yujing
AU - Zhao, Wendi
AU - Huang, Qiong
AU - Chang, Yan
AU - Wang, Qingtong
AU - Sun, Wuyi
AU - Wei, Wei
PY - 2013/12/1
Y1 - 2013/12/1
N2 - The angiotensin II type 1 receptor (AT1R) blocker losartan ameliorates rheumatoid arthritis (RA) in an experimental model. In RA, AT2R mainly opposes AT1R, but the mechanism by which this occurs still remains obscure. In the present study, we investigated the role of AT2R in the treatment of rats with adjuvant-induced arthritis (AIA) by losartan. Adjuvant-induced arthritis rats were treated with losartan (5, 10 and 15 mg/kg) and methotrexate (MTX; 0.5 mg/kg) in vivo from day 14 to day 28. Arthritis was evaluated by the arthritis index and histological examination. Angiotensin II, tumour necrosis factor-α, and VEGF levels were examined by ELISA. The expression of AT1R and AT2R was detected by western blot and immunohistochemistry analysis. After stimulation with interleukin-1β in vitro, the effects of the AT2R agonist CGP42112 (10-8-10-5 M) on the chemotaxis of monocytes induced by 10% foetal calf serum (FCS) were analysed by using Transwell assay. Subsequently, the therapeutic effects of CGP42112 (5, 10 and 20 μg/kg) were evaluated in vivo by intra-articular injection in AIA rats. After treatment with losartan, the down-regulation of AT1R expression and up-regulation of AT2R expression in the spleen and synovium of AIA rats correlated positively with reduction in the polyarthritis index. Treatment with CGP42112 inhibited the chemotaxis of AIA monocytes in vitro, possibly because of the up-regulation of AT2R expression. Intra-articular injection with CGP42112 (10 and 20 μg/kg) ameliorated the arthritis index and histological signs of arthritis. In summary, the present study strongly suggests that the up-regulation of AT2R might be an additional mechanism by which losartan exerts its therapeutic effects in AIA rats.
AB - The angiotensin II type 1 receptor (AT1R) blocker losartan ameliorates rheumatoid arthritis (RA) in an experimental model. In RA, AT2R mainly opposes AT1R, but the mechanism by which this occurs still remains obscure. In the present study, we investigated the role of AT2R in the treatment of rats with adjuvant-induced arthritis (AIA) by losartan. Adjuvant-induced arthritis rats were treated with losartan (5, 10 and 15 mg/kg) and methotrexate (MTX; 0.5 mg/kg) in vivo from day 14 to day 28. Arthritis was evaluated by the arthritis index and histological examination. Angiotensin II, tumour necrosis factor-α, and VEGF levels were examined by ELISA. The expression of AT1R and AT2R was detected by western blot and immunohistochemistry analysis. After stimulation with interleukin-1β in vitro, the effects of the AT2R agonist CGP42112 (10-8-10-5 M) on the chemotaxis of monocytes induced by 10% foetal calf serum (FCS) were analysed by using Transwell assay. Subsequently, the therapeutic effects of CGP42112 (5, 10 and 20 μg/kg) were evaluated in vivo by intra-articular injection in AIA rats. After treatment with losartan, the down-regulation of AT1R expression and up-regulation of AT2R expression in the spleen and synovium of AIA rats correlated positively with reduction in the polyarthritis index. Treatment with CGP42112 inhibited the chemotaxis of AIA monocytes in vitro, possibly because of the up-regulation of AT2R expression. Intra-articular injection with CGP42112 (10 and 20 μg/kg) ameliorated the arthritis index and histological signs of arthritis. In summary, the present study strongly suggests that the up-regulation of AT2R might be an additional mechanism by which losartan exerts its therapeutic effects in AIA rats.
KW - Adjuvant-induced arthritis
KW - Angiotensin II type 2 receptor
KW - Losartan
KW - Rheumatoid arthritis
UR - http://www.scopus.com/inward/record.url?scp=84891159115&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84891159115&partnerID=8YFLogxK
U2 - 10.1111/jcmm.12128
DO - 10.1111/jcmm.12128
M3 - Article
C2 - 24112447
AN - SCOPUS:84891159115
VL - 17
SP - 1577
EP - 1587
JO - Journal of Cellular and Molecular Medicine
JF - Journal of Cellular and Molecular Medicine
SN - 1582-1838
IS - 12
ER -