Abstract
Objective. To evaluate the effects of angiotensin II (Ang II) treatment on apoptosis of fibroblast-like synoviocytes (FLS) from patients with osteoarthritis (OA) and rheumatoid arthritis (RA). Methods. AT1 receptor expression was detected by western blotting and flow cytometry. Apoptosis induction was quantified by nucleosome ELISA and by TUNEL; cell proliferation was determined by a bromodeoxyuridine (BrdU) incorporation assay. Silencing of p65 NF-κB was obtained by using a specific siRNA. Caspase 3 activation was evaluated by a colorimetric assay and its cleavage by western blotting. Results. AT1 expression resulted comparable in FLS from OA and RA patients. Ang II pre-treatment reduced FLS apoptotic response to serum starvation and nitric oxide (NO) exposure. This protective effect was reverted in the presence of the AT1 receptor antagonist losartan as well as after silencing the expression of NF-κB. Moreover, FLS treatment with the caspase inhibitor z-VAD-fmk cancelled this Ang II effect on apoptosis. Caspase 3 activation was reduced in presence of Ang II. Conclusions. Ang II could represent an important mediator involved in FLS expansion, reducing their capacity to undergo apoptosis, through the activation of NF-κB and the blockage of caspase cascade.
| Original language | English |
|---|---|
| Pages (from-to) | 1252-1257 |
| Number of pages | 6 |
| Journal | Rheumatology |
| Volume | 46 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - Aug 2007 |
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Keywords
- Angiotensin II
- Apoptosis
- Fibroblast-like synoviocytes
- NF-κB
- Osteoarthritis
- Rheumatoid arthritis
ASJC Scopus subject areas
- Neuroscience(all)
- Rheumatology
Cite this
Angiotensin II protects fibroblast-like synoviocytes from apoptosis via the AT1-NF-κB pathway. / Pattacini, L.; Casali, B.; Boiardi, L.; Pipitone, N.; Albertazzi, L.; Salvarani, Carlo.
In: Rheumatology, Vol. 46, No. 8, 08.2007, p. 1252-1257.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Angiotensin II protects fibroblast-like synoviocytes from apoptosis via the AT1-NF-κB pathway
AU - Pattacini, L.
AU - Casali, B.
AU - Boiardi, L.
AU - Pipitone, N.
AU - Albertazzi, L.
AU - Salvarani, Carlo
PY - 2007/8
Y1 - 2007/8
N2 - Objective. To evaluate the effects of angiotensin II (Ang II) treatment on apoptosis of fibroblast-like synoviocytes (FLS) from patients with osteoarthritis (OA) and rheumatoid arthritis (RA). Methods. AT1 receptor expression was detected by western blotting and flow cytometry. Apoptosis induction was quantified by nucleosome ELISA and by TUNEL; cell proliferation was determined by a bromodeoxyuridine (BrdU) incorporation assay. Silencing of p65 NF-κB was obtained by using a specific siRNA. Caspase 3 activation was evaluated by a colorimetric assay and its cleavage by western blotting. Results. AT1 expression resulted comparable in FLS from OA and RA patients. Ang II pre-treatment reduced FLS apoptotic response to serum starvation and nitric oxide (NO) exposure. This protective effect was reverted in the presence of the AT1 receptor antagonist losartan as well as after silencing the expression of NF-κB. Moreover, FLS treatment with the caspase inhibitor z-VAD-fmk cancelled this Ang II effect on apoptosis. Caspase 3 activation was reduced in presence of Ang II. Conclusions. Ang II could represent an important mediator involved in FLS expansion, reducing their capacity to undergo apoptosis, through the activation of NF-κB and the blockage of caspase cascade.
AB - Objective. To evaluate the effects of angiotensin II (Ang II) treatment on apoptosis of fibroblast-like synoviocytes (FLS) from patients with osteoarthritis (OA) and rheumatoid arthritis (RA). Methods. AT1 receptor expression was detected by western blotting and flow cytometry. Apoptosis induction was quantified by nucleosome ELISA and by TUNEL; cell proliferation was determined by a bromodeoxyuridine (BrdU) incorporation assay. Silencing of p65 NF-κB was obtained by using a specific siRNA. Caspase 3 activation was evaluated by a colorimetric assay and its cleavage by western blotting. Results. AT1 expression resulted comparable in FLS from OA and RA patients. Ang II pre-treatment reduced FLS apoptotic response to serum starvation and nitric oxide (NO) exposure. This protective effect was reverted in the presence of the AT1 receptor antagonist losartan as well as after silencing the expression of NF-κB. Moreover, FLS treatment with the caspase inhibitor z-VAD-fmk cancelled this Ang II effect on apoptosis. Caspase 3 activation was reduced in presence of Ang II. Conclusions. Ang II could represent an important mediator involved in FLS expansion, reducing their capacity to undergo apoptosis, through the activation of NF-κB and the blockage of caspase cascade.
KW - Angiotensin II
KW - Apoptosis
KW - Fibroblast-like synoviocytes
KW - NF-κB
KW - Osteoarthritis
KW - Rheumatoid arthritis
UR - http://www.scopus.com/inward/record.url?scp=34547830802&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34547830802&partnerID=8YFLogxK
U2 - 10.1093/rheumatology/kem092
DO - 10.1093/rheumatology/kem092
M3 - Article
C2 - 17526929
AN - SCOPUS:34547830802
VL - 46
SP - 1252
EP - 1257
JO - Rheumatology
JF - Rheumatology
SN - 1462-0324
IS - 8
ER -