ArticleJournal of immunology (Baltimore, Md. : 1950)2009
Role of MAPK kinase 6 in arthritis: distinct mechanism of action in inflammation and cytokine expression.
Article in Journal of immunology (Baltimore, Md. : 1950), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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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
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Who cites it
25 citing papers in PubMed, 42 citations in OpenAlex.
- GPR143 mediates virus-induced cytoplasmic vacuolation through the MKK6-p38 pathway in teleosts.Zoological research · 2026Article
- The Challenges of Local Intra-Articular Therapy.Medicina (Kaunas, Lithuania) · 2024Review
- Lessons From the Success and Failure of Targeted Drugs for Rheumatoid Arthritis: Perspectives for Effective Basic and Translational Research.Immune network · 2022Review
- Non-'classical' MEKs: A review of MEK3-7 inhibitors.Bioorganic & medicinal chemistry letters · 2020Review
- Restoring synovial homeostasis in rheumatoid arthritis by targeting fibroblast-like synoviocytes.Nature reviews. Rheumatology · 2020Review
- Reciprocal regulation of pro-inflammatory Annexin A2 and anti-inflammatory Annexin A1 in the pathogenesis of rheumatoid arthritis.Molecular biology reports · 2019Article
- MAP2K6 is associated with radiation resistance and adverse prognosis for locally advanced nasopharyngeal carcinoma patients.Cancer management and research · 2018Article
- Identification of potential peripheral blood diagnostic biomarkers for patients with juvenile idiopathic arthritis by bioinformatics analysis.Rheumatology international · 2017Article
- Selective Regulation of MAPK Signaling Mediates RANKL-dependent Osteoclast Differentiation.International journal of biological sciences · 2016Article
- Roles of p38α mitogen-activated protein kinase in mouse models of inflammatory diseases and cancer.The FEBS journal · 2015Review
- Article
- Differential roles of MAPK kinases MKK3 and MKK6 in osteoclastogenesis and bone loss.PloS one · 2014Article
- Differential regulation of anti-inflammatory genes by p38 MAP kinase and MAP kinase kinase 6.Journal of inflammation (London, England) · 2014Article
- Duality of fibroblast-like synoviocytes in RA: passive responders and imprinted aggressors.Nature reviews. Rheumatology · 2013Review
- Cellular targeting in autoimmunity.Current allergy and asthma reports · 2012Review
- Antiinflammatory functions of p38 in mouse models of rheumatoid arthritis: advantages of targeting upstream kinases MKK-3 or MKK-6.Arthritis and rheumatism · 2012Article
- Germinal center kinase-like kinase (GLK/MAP4K3) expression is increased in adult-onset Still's disease and may act as an activity marker.BMC medicine · 2012Article
- Decreased collagen-induced arthritis severity and adaptive immunity in MKK-6-deficient mice.Arthritis and rheumatism · 2012Article
- The p38 MAPK Pathway in Rheumatoid Arthritis: A Sideways Look.The open rheumatology journal · 2012Article
- Overexpression of Ste20-related proline/alanine-rich kinase exacerbates experimental colitis in mice.Journal of immunology (Baltimore, Md. : 1950) · 2011Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Development of p38alpha inhibitors for rheumatoid arthritis has been hindered by toxicity and limited efficacy. Therefore, we evaluated whether MKK6, an upstream kinase that regulates multiple p38 isoforms, might be an alternative therapeutic target in inflammatory arthritis. Wild-type (WT), MKK6(-/-), and MKK3(-/-) mice were administered K/BxN serum to induce arthritis. Articular expression of activated kinases and cytokines was determined by Western blot, qPCR, ELISA, and multiplex analysis. Immunoprecipitation and confocal microscopy experiments were performed to determine the subcellular location of MKK6, P-p38, and MAPKAPK2 (MK2). Arthritis scores were significantly lower in MKK6(-/-) mice compared with WT mice. Joint destruction and osteoclast differentiation were lower in MKK6(-/-), as were articular IL-6 and matrix metalloproteinase-3 expression. Phospho-p38 levels were modestly decreased in the joints of arthritic MKK6(-/-) mice compared with WT but were significantly higher than MKK3(-/-) mice. P-MK2 was low in MKK6(-/-) and MKK3(-/-) mice. Uncoupled p38 and MK2 activation was also observed in cultured, MKK6(-/-) FLS and confirmed using kinase assays. Immunoprecipitation assays and confocal microscopy showed that P-p38 and MK2 colocalized in activated WT but not MKK6(-/-) FLS. Distinct patterns of cytokine production were observed in MKK6(-/-) and MKK3(-/-) cells. MKK6 deficiency suppresses inflammatory arthritis and joint destruction, suggesting it might be a therapeutic target for inflammation. Although MKK3 and MKK6 activate the p38 pathway, they regulate distinct subsets of proinflammatory cytokines. MKK6 appears mainly to facilitate p38 and MK2 colocalization in the nucleus rather than to phosphorylate p38.
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What OpenQuestion holds
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.