ArticleArthritis and rheumatism2012
Decreased collagen-induced arthritis severity and adaptive immunity in MKK-6-deficient mice.
Article in Arthritis and rheumatism, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 20 citations in OpenAlex.
- GPR143 mediates virus-induced cytoplasmic vacuolation through the MKK6-p38 pathway in teleosts.Zoological research · 2026Article
- Advances of the small molecule drugs regulating fibroblast-like synovial proliferation for rheumatoid arthritis.Frontiers in pharmacology · 2023Review
- Evaluation of the therapeutic potential of the selective p38 MAPK inhibitor Skepinone-L and the dual p38/JNK 3 inhibitor LN 950 in experimental K/BxN serum transfer arthritis.Inflammopharmacology · 2019Article
- A Novel Animal Model of Emphysema Induced by Anti-Elastin Autoimmunity.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Suppression of MAPK11 or HIPK3 reduces mutant Huntingtin levels in Huntington's disease models.Cell research · 2017Article
- Deficiency of hyaluronan synthase 1 (Has1) results in chronic joint inflammation and widespread intra-articular fibrosis in a murine model of knee joint cartilage damage.Osteoarthritis and cartilage · 2015Article
- Differential regulation of anti-inflammatory genes by p38 MAP kinase and MAP kinase kinase 6.Journal of inflammation (London, England) · 2014Article
- Differential roles of MAPK kinases MKK3 and MKK6 in osteoclastogenesis and bone loss.PloS one · 2014Article
- Antiinflammatory functions of p38 in mouse models of rheumatoid arthritis: advantages of targeting upstream kinases MKK-3 or MKK-6.Arthritis and rheumatism · 2012Article
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
objectiveThe MAPK kinases MKK-3 and MKK-6 regulate p38 MAPK activation in inflammatory diseases such as rheumatoid arthritis (RA). Previous studies demonstrated that MKK-3 or MKK-6 deficiency inhibits K/BxN serum-induced arthritis. However, the role of these kinases in adaptive immunity-dependent models of chronic arthritis is not known. The goal of this study was to evaluate MKK-3 and MKK-6 deficiency in the collagen-induced arthritis (CIA) model.
methodsWild-type (WT), MKK-3(-/-) , and MKK-6(-/-) mice were immunized with bovine type II collagen. Disease activity was evaluated by semiquantitative scoring, histologic assessment, and micro-computed tomography. Serum anticollagen antibody levels were quantified by enzyme-linked immunosorbent assay. In vitro T cell cytokine response was measured by flow cytometry and multiplex analysis. Expression of joint cytokines and matrix metalloproteinases (MMPs) was determined by quantitative polymerase chain reaction.
resultsMKK-6 deficiency markedly reduced arthritis severity compared with that in WT mice, while the absence of MKK-3 had an intermediate effect. Joint damage was minimal in arthritic MKK-6(-/-) mice and intermediate in MKK-3(-/-) mice compared with WT mice. MKK-6(-/-) mice had modestly lower levels of pathogenic anticollagen antibodies than did WT or MKK-3(-/-) mice. In vitro T cell assays showed reduced proliferation and interleukin-17 (IL-17) production by lymph node cells from MKK-6(-/-) mice in response to type II collagen. Gene expression of synovial IL-6, MMP-3, and MMP-13 was significantly inhibited in MKK-6-deficient mice.
conclusionReduced disease severity in MKK-6(-/-) mice correlated with decreased anticollagen antibody responses, indicating that MKK-6 is a crucial regulator of inflammatory joint destruction in CIA. MKK-6 is a potential therapeutic target in complex diseases involving adaptive immune responses, such as RA.
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