ArticleJournal of immunology (Baltimore, Md. : 1950)2008
Synoviocyte innate immune responses: I. Differential regulation of interferon responses and the JNK pathway by MAPK kinases.
Article in Journal of immunology (Baltimore, Md. : 1950), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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.
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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, 42 citations in OpenAlex.
- Tankyrases positively regulate influenza A virus replication via type I interferon response.Journal of virology · 2025Article
- Plasma TNF-α Elevation in Biologic Naive Rheumatoid Arthritis Patients Belonging to a Population with New Mutations in TLR4 and CYP51A1 genes without Association with Disease-Related Antibodies Levels.International journal of molecular and cellular medicine · 2024Article
- Deferoxamine Inhibits Acute Lymphoblastic Leukemia Progression through Repression of ROS/HIF-1Journal of oncology · 2022Article
- Cross-species analysis of viral nucleic acid interacting proteins identifies TAOKs as innate immune regulators.Nature communications · 2021Article
- Identification of differentially expressed genes and pathways crosstalk analysis in Rheumatoid and Osteoarthritis using next-generation sequencing and protein-protein networks.Saudi journal of biological sciences · 2021Article
- MicroRNA-206 inhibits influenza A virus replication by targeting tankyrase 2.Cellular microbiology · 2021Article
- Article
- Astragalin Suppresses Inflammatory Responses and Bone Destruction in Mice With Collagen-Induced Arthritis and in Human Fibroblast-Like Synoviocytes.Frontiers in pharmacology · 2019Article
- SIRT1 promotes tumor-like invasion of fibroblast-like synoviocytes in rheumatoid arthritis via targeting TIMP1.Oncotarget · 2017Article
- Expression of intelectin-1 in bronchial epithelial cells of asthma is correlated with T-helper 2 (Type-2) related parameters and its function.Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology · 2017Article
- Poly(I:C) increases the expression of mPGES-1 and COX-2 in rat primary microglia.Journal of neuroinflammation · 2016Article
- Whole-Genome Expression Analysis and Signal Pathway Screening of Synovium-Derived Mesenchymal Stromal Cells in Rheumatoid Arthritis.Stem cells international · 2016Article
- Antiviral Activities of Several Oral Traditional Chinese Medicines against Influenza Viruses.Evidence-based complementary and alternative medicine : eCAM · 2015Article
- Shikonin Suppresses Human T Lymphocyte Activation through Inhibition of IKK β Activity and JNK Phosphorylation.Evidence-based complementary and alternative medicine : eCAM · 2013Article
- Calcineurin subunit B upregulates β-interferon production by phosphorylation of interferon regulatory factor 3 via Toll-like receptor 4.Cancer science · 2012Article
- c-Jun N-Terminal Kinase in Inflammation and Rheumatic Diseases.The open rheumatology journal · 2012Article
- Suppression of collagen-induced arthritis in growth arrest and DNA damage-inducible protein 45β-deficient mice.Arthritis and rheumatism · 2011Article
- SPA0355, a thiourea analogue, inhibits inflammatory responses and joint destruction in fibroblast-like synoviocytes and mice with collagen-induced arthritis.British journal of pharmacology · 2011Article
- Targeting interferon regulatory factors to inhibit activation of the type I IFN response: implications for treatment of autoimmune disorders.Cellular immunology · 2011Article
- Cytokine and catabolic enzyme expression in synovium, synovial fluid and articular cartilage of naturally osteoarthritic equine carpi.Equine veterinary journal · 2010Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
JNK is a key regulator of matrix metalloproteinase production in rheumatoid arthritis. It is regulated by two upstream kinases known as MKK4 and MKK7. Previous studies demonstrated that only MKK7 is required for cytokine-mediated JNK activation and matrix metalloproteinase expression in cultured fibroblast-like synoviocytes (FLS). However, the functions of MKK4 and MKK7 in synoviocyte innate immune responses have not been determined. TNF, peptidoglycan (PGN), and LPS stimulation led to higher and more prolonged MKK7 phosphorylation compared with MKK4 in FLS. However, this pattern was reversed in poly(I-C) stimulated cells. siRNA knockdown studies showed that TNF, PGN, and LPS-induced JNK and c-Jun phosphorylation are MKK7 dependent, while poly(I-C) responses require both MKK4 and MKK7. Poly(I-C)-induced expression of IP-10, RANTES, and IFN-beta mRNA was decreased in MKK4- or MKK7-deficient FLS. However, MKK4 and MKK7 deficiency did not affect phosphorylation of IkappaB kinase-related kinases in the TLR3 signaling pathway. MKK7, but not MKK4 deficiency, significantly decreased poly(I-C)-mediated IRF3 dimerization, DNA binding, and IFN-sensitive response element-mediated gene transcription. These results were mimicked by the JNK inhibitor SP600125, indicating that JNK can directly phosphorylate IRF3. In contrast, deficiency of either MKK4 or MKK7 decreased AP-1 transcriptional activity. Therefore, JNK is differentially regulated by MKK4 and MKK7 depending on the stimulus. MKK7 is the primary activator of JNK in TNF, LPS, and PGN responses. However, TLR3 requires both MKK4 and MKK7, with the former activating c-Jun and the latter activating both c-Jun and IRF3 through JNK-dependent mechanisms.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.