A disintegrin and metalloproteinase (ADAM)-10 as a predictive factor for tocilizumab effectiveness in rheumatoid arthritis

Isozaki, Takeo; Nishimi, Shinichiro; Nishimi, Airi; Saito, Makoto; Miwa, Yusuke; Toyoshima, Yasuko; Inagaki, Kenji; Kasama, Tsuyoshi

doi:10.1080/14397595.2016.1256025

Cited by 7 publications

(4 citation statements)

References 23 publications

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“…As sADAM10 can be released by proteolytic processing from the membrane [ 29 ], this suggests the potential for truncated isoforms to be present in CSF. Indeed, recent reports indicate the possibility that ADAM10 levels can even be measured in human serum by an enzyme-linked immunosorbent assay (ELISA; [ 40 , 41 ].…”

Section: Discussionmentioning

confidence: 99%

Levels of ADAM10 are reduced in Alzheimer’s disease CSF

Sogorb‐Esteve

García‐Ayllón

Gobom

et al. 2018

J Neuroinflammation

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BackgroundThe disintegrin metalloproteinase 10 (ADAM10) is the main α-secretase acting in the non-amyloidogenic processing of the amyloid precursor protein. This study assesses whether ADAM10 is present in cerebrospinal fluid (CSF), and whether it has potential as a biomarker for Alzheimer’s disease (AD).MethodsADAM10 was characterized in human CSF samples by immunoprecipitation and western blotting using antibodies specific for different domains of the protein and by ultracentrifugation in sucrose density gradients. Samples from AD patients (n = 20) and age-matched non-AD controls (n = 20) were characterized for classical CSF biomarkers, Aβ42, T-tau, or P-tau by ELISA, and assayed for soluble ADAM10 levels by western blotting.ResultsWe found that ADAM10 is present in human CSF as several distinct species: an immature form retaining the prodomain (proADAM10; ~ 80 kDa), a mature unprocessed full-length form (ADAM10f; ~ 55 kDa), and a truncated large soluble form released from the membrane (sADAM10; ~ 50 kDa). Fractionation by ultracentrifugation on sucrose density gradients showed that the ADAM10f and sADAM10 species form large complexes. Immunoblotting revealed a significant decrease in ADAM10f and sADAM10 in AD CSF compared to control CSF, while proADAM10 levels remained unaltered.ConclusionsSeveral forms of ADAM10 are present in CSF, mainly assembled as high-molecular weight complexes. The determination of the levels of mature forms of CSF-ADAM10 may be useful as a biomarker for AD.Electronic supplementary materialThe online version of this article (10.1186/s12974-018-1255-9) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Levels of ADAM10 are reduced in Alzheimer’s disease CSF

Sogorb‐Esteve

García‐Ayllón

Gobom

et al. 2018

J Neuroinflammation

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“…In rheumatoid arthritis, ADAM10-mediated shedding drives memory T-cell infiltration into rheumatoid joints promoting local inflammation and exacerbating joint injury 36 . Moreover, ADAM10/CX3CL1 serum levels are elevated in rheumatoid arthritis patients and positively predict treatment responsiveness to tocilizumab, a monoclonal antibody targeting the IL-6 receptor 37 . Monitoring ADAM10/CX3CL1 levels may therefore be of utility in stratifying patients who will benefit most from anti-inflammatory therapies in many pro-inflammatory diseases.…”

Section: Discussionmentioning

confidence: 99%

Targeting cardiomyocyte ADAM10 ectodomain shedding promotes survival early after myocardial infarction

et al. 2022

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After myocardial infarction the innate immune response is pivotal in clearing of tissue debris as well as scar formation, but exaggerated cytokine and chemokine secretion with subsequent leukocyte infiltration also leads to further tissue damage. Here, we address the value of targeting a previously unknown a disintegrin and metalloprotease 10 (ADAM10)/CX3CL1 axis in the regulation of neutrophil recruitment early after MI. We show that myocardial ADAM10 is distinctly upregulated in myocardial biopsies from patients with ischemia-driven cardiomyopathy. Intriguingly, upon MI in mice, pharmacological ADAM10 inhibition as well as genetic cardiomycyte-specific ADAM10 deletion improves survival with markedly enhanced heart function and reduced scar size. Mechanistically, abolished ADAM10-mediated CX3CL1 ectodomain shedding leads to diminished IL-1β-dependent inflammation, reduced neutrophil bone marrow egress as well as myocardial tissue infiltration. Thus, our data shows a conceptual insight into how acute MI induces chemotactic signaling via ectodomain shedding in cardiomyocytes.

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“…The CCR2/CCl2 complex on monocytes triggers their recruitment from the bone marrow into the bloodstream. The CX3CL1 production by FLSs is supported by disintegrin and metalloproteinase domain-containing protein 10 and disintegrin; therefore, they mediate the monocyte migration in RA [79].…”

Section: Monocyte Transport To the Ra Synovial Tissuementioning

confidence: 99%

Target Role of Monocytes as Key Cells of Innate Immunity in Rheumatoid Arthritis

Salnikova,

Nikiforov,

Postnov

et al. 2024

Diseases

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Rheumatoid arthritis (RA) is a chronic, systemic, and inflammatory autoimmune condition characterized by synovitis, pannus formation (with adjacent bone erosion), and joint destruction. In the perpetuation of RA, fibroblast-like synoviocytes (FLSs), macrophages, B cells, and CD4+ T-cells—specifically Th1 and Th17 cells—play crucial roles. Additionally, dendritic cells, neutrophils, mast cells, and monocytes contribute to the disease progression. Monocytes, circulating cells primarily derived from the bone marrow, participate in RA pathogenesis. Notably, CCR2 interacts with CCL2, and CX3CR1 (expressed by monocytes) cooperates with CX3CL1 (produced by FLSs), facilitating the migration involved in RA. Canonical “classical” monocytes predominantly acquire the phenotype of an “intermediate” subset, which differentially expresses proinflammatory cytokines (IL-1β, IL-6, and TNF) and surface markers (CD14, CD16, HLA-DR, TLRs, and β1- and β2-integrins). However, classical monocytes have greater potential to differentiate into osteoclasts, which contribute to bone resorption in the inflammatory milieu; in RA, Th17 cells stimulate FLSs to produce RANKL, triggering osteoclastogenesis. This review aims to explore the monocyte heterogeneity, plasticity, antigenic expression, and their differentiation into macrophages and osteoclasts. Additionally, we investigate the monocyte migration into the synovium and the role of their cytokines in RA.

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A disintegrin and metalloproteinase (ADAM)-10 as a predictive factor for tocilizumab effectiveness in rheumatoid arthritis

Abstract: ADAM-10 may be a predictor of the effectiveness of TCZ in treating RA.

Cited by 7 publications

References 23 publications

Levels of ADAM10 are reduced in Alzheimer’s disease CSF

Levels of ADAM10 are reduced in Alzheimer’s disease CSF

Targeting cardiomyocyte ADAM10 ectodomain shedding promotes survival early after myocardial infarction

Target Role of Monocytes as Key Cells of Innate Immunity in Rheumatoid Arthritis

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