Angiotensin II protects fibroblast-like synoviocytes from apoptosis via the AT1-NF-κB pathway

L. Pattacini, B. Casali, L. Boiardi, N. Pipitone, L. Albertazzi, Carlo Salvarani

Research output: Contribution to journalArticle

13 Citations (Scopus)

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 languageEnglish
Pages (from-to)1252-1257
Number of pages6
JournalRheumatology
Volume46
Issue number8
DOIs
Publication statusPublished - Aug 2007

Fingerprint

Angiotensin II
Fibroblasts
Apoptosis
Caspase 3
Osteoarthritis
Rheumatoid Arthritis
Western Blotting
Caspase Inhibitors
Losartan
Nucleosomes
In Situ Nick-End Labeling
Bromodeoxyuridine
Caspases
Starvation
Small Interfering RNA
Flow Cytometry
Nitric Oxide
Therapeutics
Enzyme-Linked Immunosorbent Assay
Cell Proliferation

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 journalArticle

Pattacini, L. ; Casali, B. ; Boiardi, L. ; Pipitone, N. ; Albertazzi, L. ; Salvarani, Carlo. / Angiotensin II protects fibroblast-like synoviocytes from apoptosis via the AT1-NF-κB pathway. In: Rheumatology. 2007 ; Vol. 46, No. 8. pp. 1252-1257.
@article{7612023154c6485f8e7b2480841b5814,
title = "Angiotensin II protects fibroblast-like synoviocytes from apoptosis via the AT1-NF-κB pathway",
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.",
keywords = "Angiotensin II, Apoptosis, Fibroblast-like synoviocytes, NF-κB, Osteoarthritis, Rheumatoid arthritis",
author = "L. Pattacini and B. Casali and L. Boiardi and N. Pipitone and L. Albertazzi and Carlo Salvarani",
year = "2007",
month = "8",
doi = "10.1093/rheumatology/kem092",
language = "English",
volume = "46",
pages = "1252--1257",
journal = "Rheumatology",
issn = "1462-0324",
publisher = ". Published by Oxford University Press on behalf of the British Society for Rheumatology",
number = "8",

}

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 -