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FRI0070 Angiotensin II type 2 receptor (AT2R) is overexpressed in rheumatoid arthritis and osteoarthritis synovium and increases steadily with inflammatory stimuli: a potential new target for pain and anti-inflammatory therapies
  1. R Terenzi1,
  2. M Manetti2,
  3. I Rosa2,
  4. E Romano1,
  5. F Galluccio1,
  6. S Guiducci1,
  7. L Ibba-Manneschi2,
  8. M Matucci-Cerinic1
  1. 1Department of Medicine, Division of Rheumatology
  2. 2Department of Anatomy, Università degli Studi di Firenze, Firenze, Italy

Abstract

Background Despite increasing evidence suggesting that angiotensin II type 2 receptor (AT2R) antagonism might be a feasible strategy for the treatment of chronic inflammation and pain, no study has yet analyzed the synovial expression of AT2R.

Objectives To investigate the expression of AT2R in rheumatoid arthritis (RA) and osteoarthritis (OA) synovium and its possible modulation in fibroblast-like synoviocytes (FLS) by proinflammatory stimuli.

Methods The expression of AT2R in RA and OA synovium was investigated by immunohistochemistry. AT2R expression in synovial T cells, B cells, macrophages and FLS was assessed by double immunofluorescence. FLS were isolated from healthy (H), OA and RA synovium and treated with tumor necrosis factor (TNF)-α and interleukin (IL)-1β, alone or in combination. Immunocytochemistry and Western blotting were performed to study AT2R expression in cultured FLS.

Results RA synovium showed stronger AT2R immunostaining than OA synovium in the lining and sublining layers. In RA synovium, AT2R was strongly expressed in CD3+ T cells, CD20+ B cells, CD68+ macrophages and vimentin+ FLS. High levels of AT2R were found in OA-FLS and RA-FLS at baseline, while AT2R expression was negligible in basal H-FLS. AT2R expression was higher in RA-FLS than OA-FLS. Treatment with TNF-α and IL-1β was able to foster the expression of AT2R not only in OA-FLS and RA-FLS, but also in H-FLS.

Conclusions AT2R is strongly expressed in different cell types of the inflamed synovium and proinflammatory stimuli may foster the expression of AT2R in FLS. AT2R might represent a novel potential therapeutic target in chronic arthritides.

Disclosure of Interest None declared

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