Nat. Rev. Rheumatol. doi: /nrrheum

Slides:

Advertisements

Similar presentations

Figure 1 Simplified scheme of TGFβ signalling

Advertisements

Nat. Rev. Cardiol. doi: /nrcardio

Figure 3 Connexins in cartilage

Figure 5 Involvement of B cells in SLE

Figure 3 Metabolism in homeostatic chondrocytes

Figure 1 Rheumatoid arthritis development over time in relation to the level of inflammation Figure 1 | Rheumatoid arthritis development over time in relation.

Nat. Rev. Rheumatol. doi: /nrrheum

Laurence J. Egan, M.B., William J. Sandborn, M.D

Nat. Rev. Rheumatol. doi: /nrrheum

Nat. Rev. Rheumatol. doi: /nrrheum

Figure 1 Factors underlying metabolic alterations in osteoarthritis

Nat. Rev. Rheumatol. doi: /nrrheum

Figure 1 Induction of immune tolerance

Figure 4 Simplified T cell and antigen presenting

Figure 3 Proposed mechanisms underlying the links

Figure 3 Microanatomical changes in enthesitis

Figure 4 Ex vivo synovial tissue culture viability

Nat. Rev. Rheumatol. doi: /nrrheum

Figure 5 Defects in the JAK–STAT signalling pathway

Nat. Rev. Rheumatol. doi: /nrrheum

Figure 3 Simplified EULAR and GRAPPA

Figure 2 Simplified EULAR and GRAPPA

Figure 3 Transcriptome studies performed in the target

Figure 2 Shared genetic loci in systemic autoimmune diseases

Figure 2 Three distinct mechanisms of activation of

Figure 7 Defects in apoptosis

Figure 1 Location of HLA variants known to be associated

Figure 1 CAR-T-cell design

Figure 3 Defects in the T cell receptor signalling pathway

Figure 4 Altered metabolism in chondrocytes in osteoarthritis

Nat. Rev. Rheumatol. doi: /nrrheum

Figure 3 Strategies to achieve therapeutic inhibition of IL-1

Figure 1 Pharmacodynamics of methotrexate in RA

Figure 3 Hypothetical mechanisms of smoking-associated

Nat. Rev. Rheumatol. doi: /nrrheum

Figure 2 Cas9 targeting using crRNA (CRISPR

Figure 2 Interaction effects between heterozygous HLA‑DRB1

Nat. Rev. Rheumatol. doi: /nrrheum

Figure 2 Microbiota and osteoimmunology

Figure 3 Statistical approaches for the analysis of metabolomic data

Figure 3 Cell-surface markers for NP cell differentiation

Figure 6 Lack of IRF5 causes a reduction in neutrophil influx

Figure 5 The role of Ly6Chi and Ly6Clo monocytes

Nat. Rev. Rheumatol. doi: /nrrheum

Figure 3 Multi-hit model for autoimmune diseases

Figure 1 Simplified EULAR and GRAPPA

Nat. Rev. Rheumatol. doi: /nrrheum

Nat. Rev. Rheumatol. doi: /nrrheum

Nat. Rev. Rheumatol. doi: /nrrheum

Figure 1 Research advances in osteoarthritis management

Figure 2 Emerging hallmarks of T cells in rheumatoid arthritis

Nat. Rev. Rheumatol. doi: /nrrheum

Nat. Rev. Rheumatol. doi: /nrrheum

Figure 6 Metabolism of pterins

Nat. Rev. Rheumatol. doi: /nrrheum

Nat. Rev. Rheumatol. doi: /nrrheum

Figure 1 Transmission of pain by NGF

Nat. Rev. Rheumatol. doi: /nrrheum

Laurence J. Egan, M.B., William J. Sandborn, M.D

Figure 1 Chronic inflammation and DNA damage in people with SLE

Figure 3 Nuclear-penetrating autoantibodies and synthetic lethality

Figure 2 Cellular contributions to the development of SLE

Figure 2 Phenotypes of osteoarthritis

Charles C. Caldwell, Alex B. Lentsch Gastroenterology

Figure 1 Patterns of joint and organ involvement in rheumatic disease

Nat. Rev. Rheumatol. doi: /nrrheum

Figure 1 The role of macrophages in RA

Figure 2 The main effects of adipokines on bone remodelling in osteoarthritis Figure 2 | The main effects of adipokines on bone remodelling in osteoarthritis.

Figure 5 Mechanisms of adiponectin actions in the kidney

Anti-hypoxia–A2-adenosinergic coadjuvant-mediated inhibition of the hypoxia–A2-adenosinergic pathway. Anti-hypoxia–A2-adenosinergic coadjuvant-mediated.

Presentation transcript:

Nat. Rev. Rheumatol. doi:10.1038/nrrheum.2016.175 Figure 4 Proposed mechanism by which methotrexate increases adenosine signalling Figure 4 | Proposed mechanism by which methotrexate increases adenosine signalling. Methotrexate (in particular polyglutamated methotrexate) antagonizes the activity of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) transformylase (ATIC), resulting in accumulation of AICAR, which antagonizes the activity of adenosine deaminase (ADA) and AMP deaminase (AMPDA), increasing concentrations of AMP and adenosine, which are externalized by the cell. AMP in the extracellular environment is cleaved to adenosine by the ecto-5′-nucleotidase CD73, which is potentiated by AICAR. Extracellular adenosine signals in an autocrine and paracrine fashion via adenosine receptors (ADOR). FAICAR, 5-formamidoimidazole-4-carboxamide ribotide. Brown, P. M. et al. (2016) Mechanism of action of methotrexate in rheumatoid arthritis, and the search for biomarkers Nat. Rev. Rheumatol. doi:10.1038/nrrheum.2016.175