ArticleAnnals of the rheumatic diseases2007
Predominant activation of MAP kinases and pro-destructive/pro-inflammatory features by TNF alpha in early-passage synovial fibroblasts via TNF receptor-1: failure of p38 inhibition to suppress matrix metalloproteinase-1 in rheumatoid arthritis.
Article in Annals of the rheumatic diseases, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- Pooled it
- Visfatin/pre-B-cell colony-enhancing factor (PBEF), a proinflammatory and cell motility-changing factor in rheumatoid arthritis.The Journal of biological chemistry · 2012Trial
- LIN28A‒let-7b axis drives the aggressive and proinflammatory phenotype of rheumatoid arthritis fibroblast-like synoviocytes.Arthritis research & therapy · 2026Article
- Extracellular matrix remodeling in the pathogenesis and therapeutic strategies of rheumatoid arthritis.Clinical and experimental medicine · 2026Review
- Luteal fibroblasts produce prostaglandins in response to IL1β in a MAPK-mediated manner.Molecular and cellular endocrinology · 2025Article
- Exploring Platelet-Rich Plasma Therapy for Knee Osteoarthritis: An In-Depth Analysis.Journal of functional biomaterials · 2024Review
- Addressing Knee Osteoarthritis Pathology Through Platelet-Rich Plasma Treatment: A Comprehensive Review.Advances in orthopedics · 2024Review
- Complement Regulation in Immortalized Fibroblast-like Synoviocytes and Primary Human Endothelial Cells in Response to SARS-CoV-2 Nucleocapsid Protein and Pro-Inflammatory Cytokine TNFα.Life (Basel, Switzerland) · 2022Article
- Regulatory role of KCa3.1 in immune cell function and its emerging association with rheumatoid arthritis.Frontiers in immunology · 2022Review
- Low-Frequency Vibration Promotes Tumor Necrosis Factor-α Production to Increase Cartilage Degeneration in Knee Osteoarthritis.Cartilage · 2021Article
- The inhibition of Src kinase suppresses the production of matrix metalloproteinases in from synovial fibroblasts and inhibits MAPK and STATs pathwaysTurkish journal of medical sciences · 2021Article
- TNF in the era of immune checkpoint inhibitors: friend or foe?Nature reviews. Rheumatology · 2021Review
- Cellular electrophysiological principles that modulate secretion from synovial fibroblasts.The Journal of physiology · 2017Review
- Article
- Activated protein C inhibits proliferation and tumor necrosis factor α-stimulated activation of p38, c-Jun NH2-terminal kinase (JNK) and Akt in rheumatoid synovial fibroblasts.Molecular medicine (Cambridge, Mass.) · 2013Article
- Death-associated protein kinase controls STAT3 activity in intestinal epithelial cells.The American journal of pathology · 2013Article
- IL-33 regulates TNF-α dependent effects in synovial fibroblasts.International journal of molecular medicine · 2012Article
- Selective involvement of ERK and JNK mitogen-activated protein kinases in early rheumatoid arthritis (1987 ACR criteria compared to 2010 ACR/EULAR criteria): a prospective study aimed at identification of diagnostic and prognostic biomarkers as well as therapeutic targets.Annals of the rheumatic diseases · 2012Article
- Inhibition of MAP kinase in synovium by treatment with tocilizumab in rheumatoid arthritis.Clinical rheumatology · 2011Article
- Inhibition of inflammatory mediators and related signaling pathways by macrophage-stimulating protein in rheumatoid arthritis synovial fibroblasts.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveTo examine the relative importance of tumour necrosis factor-receptor 1 (TNF-R1) and TNF-R2 and their signalling pathways for pro-inflammatory and pro-destructive features of early-passage synovial fibroblasts (SFB) from rheumatoid arthritis (RA) and osteoarthritis (OA).
methodsCells were stimulated with tumour necrosis factor (TNF)alpha or agonistic anti-TNF-R1/TNF-R2 monoclonal antibodies. Phosphorylation of p38, ERK and JNK kinases was assessed by western blot; proliferation by bromodesoxyuridine incorporation; interleukin (IL)6, IL8, prostaglandin E(2) (PGE(2)) and matrix metalloproteinase (MMP)-1 secretion by ELISA; and MMP-3 secretion by western blot. Functional assays were performed with or without inhibition of p38 (SB203580), ERK (U0126) or JNK (SP600125).
resultsIn RA- and OA-SFB, TNFalpha-induced phosphorylation of p38, ERK or JNK was exclusively mediated by TNF-R1. Reduction of proliferation and induction of IL6, IL8 and MMP-1 were solely mediated by TNF-R1, whereas PGE(2) and MMP-3 secretion was mediated by both TNF-Rs. In general, inhibition of ERK or JNK did not significantly alter the TNFalpha influence on these effector molecules. In contrast, inhibition of p38 reversed TNFalpha effects on proliferation and IL6/PGE(2) secretion (but not on IL8 and MMP-3 secretion). The above effects were comparable in RA- and OA-SFB, except that TNFalpha-induced MMP-1 secretion was reversed by p38 inhibition only in OA-SFB.
conclusionIn early-passage RA/OA-SFB, activation of MAPK cascades and pro-inflammatory/pro-destructive features by TNFalpha is predominantly mediated by TNF-R1 and, for proliferation and IL6/PGE(2) secretion, exclusively regulated by p38. Strikingly, RA-SFB are insensitive to p38 inhibition of MMP-1 secretion. This indicates a resistance of RA-SFB to the inhibition of pro-destructive functions and suggests underlying structural/functional alterations of the p38 pathway, which may contribute to the pathogenesis or therapeutic sensitivity of RA, or both.
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Registered trials
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