Low levels of apoptosis and high FLIP expression in early rheumatoid arthritis synovium - PubMed (original) (raw)
Low levels of apoptosis and high FLIP expression in early rheumatoid arthritis synovium
A I Catrina et al. Ann Rheum Dis. 2002 Oct.
Abstract
Objectives: To define synovial apoptosis with respect to disease duration, inflammatory cell type, FLIP (FLICE-like inhibitory protein), and cytokines expression in patients with rheumatoid arthritis (RA).
Methods: Synovial biopsy specimens from 11 patients with longstanding RA (median disease duration 21 years) and eight with early RA (median disease duration five months) were investigated. Apoptosis (TUNEL method combined with morphological analysis), cell surface markers (CD3, CD68), cytokines (interleukin (IL) 1alpha, IL1beta, tumour necrosis factor alpha, and IL6), and FLIP expression were evaluated. Computer assisted image analysis was used for quantification.
Results: The apoptosis level in RA synovium was significantly higher in the group of patients with longstanding RA than in the patients with early RA (8.8% v 0.6%, p=0.001), while the number of macrophages and FLIP expression were higher in the group with early disease than in the group with longstanding RA (16.2% v 8.3%, p=0.02 and 31.1% v 0.2%, p=0.001 respectively). All three markers correlated significantly with disease duration (R=-0.7, p<0.001 for FLIP, R=0.6, p=0.001 for apoptosis, and R=-0.5, p<0.05 for CD68). Cytokine expression and T cell score were not significantly different in early RA from longstanding RA. No differences were seen between patients treated or not treated with corticosteroids or between patients treated or not treated with disease modifying antirheumatic drugs.
Conclusions: The findings suggest that RA synovial macrophages are resistant to apoptosis in early RA and express high levels of FLIP. During natural or drug modified disease progression the apoptotic mechanism may be restored with a specific increase of synovial apoptosis in patients with longstanding arthritis.
Figures
Figure 1
Brown (diaminobenzidine) immunoperoxidase staining for TUNEL, CD68, and FLIP positive cells in serial sections from frozen synovial biopsy specimens counterstained with haematoxylin. (A) TUNEL in early RA (case 1); (B) TUNEL in longstanding RA (case 2); (C) CD68 in early RA (case 1); (D) CD68 in longstanding RA (case 2); (E) FLIP in early RA (case 1); (F) FLIP in longstanding RA (case 2). Original magnification x340, the bar represent 15 µm.
Figure 2
Differences between apoptosis, CD68, and FLIP expression in early compared with longstanding RA. Horizontal lines represent median values and whiskers the non-outliers values. Statistical analysis was performed using the non-parametric Mann-Whitney U test. *p<0.05; **p<0.01.
Similar articles
- Differential regulation of Fas-mediated apoptosis of rheumatoid synoviocytes by tumor necrosis factor alpha and basic fibroblast growth factor is associated with the expression of apoptosis-related molecules.
Kobayashi T, Okamoto K, Kobata T, Hasunuma T, Kato T, Hamada H, Nishioka K. Kobayashi T, et al. Arthritis Rheum. 2000 May;43(5):1106-14. doi: 10.1002/1529-0131(200005)43:5<1106::AID-ANR21>3.0.CO;2-F. Arthritis Rheum. 2000. PMID: 10817565 - FLICE-inhibitory protein expression in synovial fibroblasts and at sites of cartilage and bone erosion in rheumatoid arthritis.
Schedel J, Gay RE, Kuenzler P, Seemayer C, Simmen B, Michel BA, Gay S. Schedel J, et al. Arthritis Rheum. 2002 Jun;46(6):1512-8. doi: 10.1002/art.10309. Arthritis Rheum. 2002. PMID: 12115181 - What can we learn from the synovium in early rheumatoid arthritis?
Katrib A, McNeil HP, Youssef PP. Katrib A, et al. Inflamm Res. 2002 Apr;51(4):170-5. doi: 10.1007/pl00012390. Inflamm Res. 2002. PMID: 12058953 Review. - Apoptosis in rheumatoid arthritis.
Baier A, Meineckel I, Gay S, Pap T. Baier A, et al. Curr Opin Rheumatol. 2003 May;15(3):274-9. doi: 10.1097/00002281-200305000-00015. Curr Opin Rheumatol. 2003. PMID: 12707581 Review.
Cited by
- An engineered construct of cFLIP provides insight into DED1 structure and interactions.
Panaitiu AE, Basiashvili T, Mierke DF, Pellegrini M. Panaitiu AE, et al. Structure. 2022 Feb 3;30(2):229-239.e5. doi: 10.1016/j.str.2021.10.011. Epub 2021 Nov 19. Structure. 2022. PMID: 34800372 Free PMC article. - Cell death in chronic inflammation: breaking the cycle to treat rheumatic disease.
Anderton H, Wicks IP, Silke J. Anderton H, et al. Nat Rev Rheumatol. 2020 Sep;16(9):496-513. doi: 10.1038/s41584-020-0455-8. Epub 2020 Jul 8. Nat Rev Rheumatol. 2020. PMID: 32641743 Review. - Synovial interlukin-6 affects apoptosis induction via nuclear factor kappa-B and fractalkine pathway during adjuvant arthritis.
Golabi S, Zaringhalam J, Manaheji H. Golabi S, et al. Med J Islam Repub Iran. 2020 Mar 25;34:25. doi: 10.34171/mjiri.34.25. eCollection 2020. Med J Islam Repub Iran. 2020. PMID: 32551314 Free PMC article. - Intracellular apoptotic pathways: a potential target for reducing joint damage in rheumatoid arthritis.
Williams B, Dharmapatni A, Crotti T. Williams B, et al. Inflamm Res. 2018 Mar;67(3):219-231. doi: 10.1007/s00011-017-1116-5. Epub 2017 Nov 21. Inflamm Res. 2018. PMID: 29164267 Review. - The inflammatory role of phagocyte apoptotic pathways in rheumatic diseases.
Cuda CM, Pope RM, Perlman H. Cuda CM, et al. Nat Rev Rheumatol. 2016 Aug 23;12(9):543-58. doi: 10.1038/nrrheum.2016.132. Nat Rev Rheumatol. 2016. PMID: 27549026 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical