ArticleArthritis research & therapy2009
Suppressive effect of secretory phospholipase A2 inhibitory peptide on interleukin-1beta-induced matrix metalloproteinase production in rheumatoid synovial fibroblasts, and its antiarthritic activity in hTNFtg mice.
Article in Arthritis research & therapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 20 citations in OpenAlex.
- Cytosolic phospholipase A2 as a therapeutic target for degenerative joint diseases.Bone research · 2025Article
- Human iPSC-based disease modeling studies identify a common mechanistic defect and potential therapies for AMD and related macular dystrophies.Developmental cell · 2024Article
- Multimodal regulation of the osteoclastogenesis process by secreted group IIA phospholipase AFrontiers in cell and developmental biology · 2022Article
- Insights on the molecular mechanism of anti-inflammatory effect of formula from Islamic traditional medicine: An in-silico study.Journal of traditional and complementary medicine · 2019Article
- Simiao Pill Attenuates Collagen-Induced Arthritis in Rats through Suppressing the ATX-LPA and MAPK Signalling Pathways.Evidence-based complementary and alternative medicine : eCAM · 2019Article
- Activated protein C binds directly to Tie2: possible beneficial effects on endothelial barrier function.Cellular and molecular life sciences : CMLS · 2017Article
- Role of the NLRP3 inflammasome in the transient release of IL-1β induced by monosodium urate crystals in human fibroblast-like synoviocytes.Journal of inflammation (London, England) · 2015Article
- MMP-9 from sublethally irradiated tumor promotes Lewis lung carcinoma cell invasiveness and pulmonary metastasis.Oncogene · 2012Article
- Celecoxib: considerations regarding its potential disease-modifying properties in osteoarthritis.Arthritis research & therapy · 2011Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionSecretory phospholipase A2 (sPLA2) and matrix metalloproteinase (MMP) inhibitors are potent modulators of inflammation with therapeutic potential, but have limited efficacy in rheumatoid arthritis (RA). The objective of this study was to understand the inhibitory mechanism of phospholipase inhibitor from python (PIP)-18 peptide in cultured synovial fibroblasts (SF), and to evaluate its therapeutic potential in a human tumor necrosis factor (hTNF)-driven transgenic mouse (Tg197) model of arthritis.
methodsGene and protein expression of sPLA2-IIA, MMP-1, MMP-2, MMP-3, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1, and TIMP-2 were analyzed by real time PCR and ELISA respectively, in interleukin (IL)-1beta stimulated rheumatoid arthritis (RA) and osteoarthritis (OA) synovial fibroblasts cells treated with or without inhibitors of sPLA2 (PIP-18, LY315920) or MMPs (MMP Inhibitor II). Phosphorylation status of mitogen-activated protein kinase (MAPK) proteins was examined by cell-based ELISA. The effect of PIP-18 was compared with that of celecoxib, methotrexate, infliximab and antiflamin-2 in Tg197 mice after ip administration (thrice weekly for 5 weeks) at two doses (10, 30 mg/kg), and histologic analysis of ankle joints. Serum sPLA2 and cytokines (tumor necrosis factor (TNF)alpha, IL-6) were measured by Escherichia coli (E coli) assay and ELISA, respectively.
resultsPIP-18 inhibited sPLA2-IIA production and enzymatic activity, and suppressed production of MMPs in IL-1beta-induced RA and OA SF cells. Treatment with PIP-18 blocked IL-1beta-induced p38 MAPK phosphorylation and resulted in attenuation of sPLA2-IIA and MMP mRNA transcription in RA SF cells. The disease modifying effect of PIP-18 was evidenced by significant abrogation of synovitis, cartilage degradation and bone erosion in hTNF Tg197 mice.
conclusionsOur results demonstrate the benefit that can be gained from using sPLA2 inhibitory peptide for RA treatment, and validate PIP-18 as a potential therapeutic in a clinically relevant animal model of human arthritis.
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