Among human macrophages polarised to different phenotypes, the M-CSF-oriented cells present the highest pro-inflammatory response to the rheumatoid arthritis-specific immune complexes containing ACPA

Clavel, C; Ceccato, Laurie; Anquetil, Florence; Serre, Guy; Sebbag, Mireille

doi:10.1136/annrheumdis-2015-208887

Cited by 45 publications

(38 citation statements)

References 54 publications

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“…had increased expression of CD64, when in fact the M2 had decreased expression. The increase in CD32 with the addition of IL-4 is in contrast to studies on macrophages derived from blood monocytes, which indicate that IL-10 but not IL-4 increases its expression [27].…”

Section: Thp-1 Macrophage Extracellular Marker Expression After Phenocontrasting

confidence: 85%

Similarities and differences in surface receptor expression by THP-1 monocytes and differentiated macrophages polarized using seven different conditioning regimens

Forrester

Wassall

Hall

et al. 2018

Cellular Immunology

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Macrophages are key in orchestrating immune responses to micro-environmental stimuli, sensed by a complex set of surface receptors. The human cell line THP-1 has a monocytic phenotype, including the ability to differentiate into macrophages, providing a tractable, standardised surrogate for human monocyte-derived macrophages. Here we assessed the expression of 49 surface markers including Fc, complement, C-type lectin and scavenger receptors; TIMs; Siglecs; and co-stimulatory molecules by flow cytometry on both THP-1 monocytes and macrophages and following macrophage activation with seven standard conditioning/polarizing stimuli. Of the 34 surface markers detected on macrophages, 18 altered expression levels on activation. From these, expression of 9 surface markers were consistently altered by all conditioning regimens, while 9 were specific to individual polarizing stimuli. This study provides a resource for the study of macrophages and highlights that macrophage polarization states share much in common and the differences do not easily fit a simple classification system.

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Section: Thp-1 Macrophage Extracellular Marker Expression After Phenocontrasting

confidence: 85%

Similarities and differences in surface receptor expression by THP-1 monocytes and differentiated macrophages polarized using seven different conditioning regimens

Forrester

Wassall

Hall

et al. 2018

Cellular Immunology

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“…However, studies by Tsuneyoshi et al [35] in human RA synovial tissue demonstrated mixed patterns of FRβ expression on ‘M1’ (‘pro-inflammatory’) and M2 macrophages. In this context it is also important to note that M2 macrophages in an RA environment with complex IgG autoantibodies and/or ACPA antibodies are triggered to produce pro-inflammatory cytokines [36, 37]. Thus, MTX targeting with respect to polarization of macrophages and the role of FRβ therein warrant further investigations.…”

Section: Discussionmentioning

confidence: 99%

In-vivo monitoring of anti-folate therapy in arthritic rats using [18F]fluoro-PEG-folate and positron emission tomography

et al. 2017

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BackgroundFolate receptor β (FRβ) is involved in facilitating cellular uptake of folates and anti-folates (such as methotrexate (MTX)). In rheumatoid arthritis, FRβ is expressed on synovial macrophages and recently has been explored as a biomarker for imaging in arthritic rats using the folate-based positron emission tomography (PET) tracer [18F]fluoro-PEG-folate. The purpose of this study was to examine whether this folate tracer can also be used to monitor therapeutic efficacy of MTX in arthritic rats.MethodsArthritic rats received either no treatment or MTX therapy (1 mg/kg, either 2× or 4×). Healthy rats did not receive any arthritic induction or therapy. [18F]fluoro-PEG-folate PET-CT scans (60 min) were performed before and after MTX therapy. Following PET, the ex-vivo tissue distribution of radioactivity was determined in excised knees and multiple tissues. Synovial macrophage infiltration in knee sections was quantified by immunohistochemistry using ED1 and ED2 antibodies.ResultsPET scans clearly visualized increased uptake of [18F]fluoro-PEG-folate in arthritic knees compared with contralateral knees. Significantly lower standard uptake values (1.5-fold, p < 0.01) were observed in arthritic knees of both MTX-treated groups after therapy, approximating the levels seen in healthy rats. Consistently, ex-vivo tissue distribution demonstrated a 2–4-fold lower tracer uptake in the arthritic knee of 2× and 4× MTX-treated rats, respectively, compared with control rats. These results were corroborated with significantly reduced (2–4-fold, p < 0.01) ED1-positive and ED2-positive synovial macrophages in arthritic knees of the MTX-treated rats compared with those of the control rats.ConclusionThis study in arthritic rats underscores the potential and usefulness of [18F]fluoro-PEG-folate PET as a therapeutic monitoring tool of MTX therapy and potentially other anti-folate treatment of arthritis.

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“…Among pro-inflammatory cytokines, TNF-α is the master element of inflammation ( McInnes and Schett, 2011 ), and IL-6 and IL-1β are downstream mediators of TNF-α ( Zheng et al, 2014 ), which together play a critical role in mediating synovitis and joint destruction in RA ( Xin et al, 2014 ). Among activated immune cells in RA, macrophages, which produce TNF-α, IL-6 and IL-1β ( Zheng et al, 2014 ; Clavel et al, 2016 ) and tissue-degrading enzymes in the inflammatory infiltrate synovial sublining and at the pannus-cartilage interface ( Davignon et al, 2013 ; Yeo et al, 2016 ), are central players in the pathogenesis ( Szekanecz and Koch, 2007 ) and are an ideal target for the treatment of RA ( Davignon et al, 2013 ). Biologicals blocking TNF-α, IL-6 and IL-1 are currently used in clinic with therapeutic potential ( Smolen et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

“…In RA, macrophages are the key effector cells in the acute and chronic phases by secreting pro-inflammatory cytokines and mediators that drive angiogenesis, infiltration by immune cells, and cartilage and bone destruction ( Clavel et al, 2016 ). Macrophage number increase in the inflamed synovium due to expansion of resident macrophages and infiltration by circulating monocytes ( Hamilton and Tak, 2009 ).…”

Section: Introductionmentioning

confidence: 99%

Tamarixinin A Alleviates Joint Destruction of Rheumatoid Arthritis by Blockade of MAPK and NF-κB Activation

Zhuang

Liu

et al. 2017

Front. Pharmacol.

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Background: Tamarixinin A, a natural tannin isolated from Myricaria bracteata, has been confirmed to have moderate anti-inflammatory effects in vitro and in vivo. However, how it effects rheumatoid arthritis (RA) is still unknown. Therefore, the aim of this study is to investigate the therapeutic effects of tamarixinin A on experimental RA, and explore the underlying mechanism.Methods: The anti-arthritic effects of tamarixinin A were evaluated on collagen-induced arthritis (CIA) mice and adjuvant-induced arthritis (AIA) rats. The hind paw thickness, inflammatory cytokine levels in serum, and histopathological assessments were determined. The arthritis score was evaluated. Activation of p38 and p65 in AIA rats was also determined. The anti-inflammatory effect in vitro was also tested in LPS induced macrophages, and its related anti-inflammatory signaling pathways were explored.Results: Treatment with tamarixinin A significantly suppressed the progression and development of RA in CIA mice and AIA rats. Both in CIA mice and AIA rats, arthritis scores decreased, paw swelling and thickness were reduced, and joint destruction was alleviated. In AIA rats, tamarixinin A significantly inhibited the expression of p38, p-p38 and p65. In addition, tamarixinin A inhibited the production of pro-inflammatory mediators, the phosphorylation of p38, ERK, JNK and p65, as well as the nuclear translocation of p38 in LPS- induced macrophages.Conclusion: Tamarixinin A is a potential effective candidate compound for human RA treatment, which executes anti-arthritic effects potentially through down-regulating MAPK and NF-κB signal pathway activation.

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Among human macrophages polarised to different phenotypes, the M-CSF-oriented cells present the highest pro-inflammatory response to the rheumatoid arthritis-specific immune complexes containing ACPA

Cited by 45 publications

References 54 publications

Similarities and differences in surface receptor expression by THP-1 monocytes and differentiated macrophages polarized using seven different conditioning regimens

Similarities and differences in surface receptor expression by THP-1 monocytes and differentiated macrophages polarized using seven different conditioning regimens

In-vivo monitoring of anti-folate therapy in arthritic rats using [18F]fluoro-PEG-folate and positron emission tomography

Tamarixinin A Alleviates Joint Destruction of Rheumatoid Arthritis by Blockade of MAPK and NF-κB Activation

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