Abstract:
BACKGROUND:Toll-like receptors (TLRs) and macrophages play an important role in rheumatoid arthritis (RA). Currently, it is not clear whether inflammatory M1 or anti-inflammatory M2 predominate among the resident macrophages in the synovium. In the present study, we set out to investigate the impact of TLR stimulation on monocyte-derived M1 and M2 macrophage function and phenotype by mimicking the exposure to abundant TLR agonists as occurs in the context of RA. The response of macrophage subsets to TLR2 and TLR4 activation was evaluated on cluster of differentiation (CD) marker profile; cytokine secretion; gene expression; and NF-κB, interferon regulatory factors 3 and 7 (IRF3/7), and mitogen-activated protein kinase (MAPK) activation. METHODS:Human monocytes were isolated from peripheral blood of healthy individuals and patients with RA and differentiated into M1-like and M2-like macrophages by granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF), respectively. Cells were either (1) stimulated with TLR ligands Pam3 or lipopolysaccharide (LPS) or (2) classically activated via interferon (IFN)-γ/LPS. Cytokine production was measured by enzyme-linked immunosorbent assay, and gene expression was measured by qPCR. Cells were stained for CD markers and analyzed by fluorescence-activated cell sorting. NF-κB, IRF3/7, and MAPKs were detected by Western blotting. RESULTS:Monocyte-derived macrophages of healthy donors (HD) or patients with RA displayed comparable subset-specific phenotypes upon exposure to TLR agonists. CD14 and CD163 marker expression on M2 macrophages did not change upon TLR2 and TLR4 engagement. By contrast, M2 gene markers HMOX1, FOLR2, and SLC40A1 were decreased. Importantly, M2 macrophages derived from HD or patients with RA showed both a decreased ratio of interleukin (IL)-10/IL-6 and IL-10/IL-8 upon stimulation with TLR2 ligand Pam3 compared with TLR4 ligand LPS. Gene expression of TLR2 was increased, whereas TLR4 expression was decreased, by TLR ligand stimulation. MAPKs p38, extracellular signal-regulated kinase 1/2, and c-Jun N-terminal kinase were activated more strongly in M2 than in M1 macrophages by Pam3 or LPS. CONCLUSIONS:We show that the anti-inflammatory activity of M2 macrophages is reduced in the presence of abundant TLR2 ligands without significant changes in cell surface markers. Thus, the classical M1/M2 paradigm based on cellular markers does not apply to macrophage functions in inflammatory conditions such as RA.
journal_name
Arthritis Res Therjournal_title
Arthritis research & therapyauthors
Quero L,Hanser E,Manigold T,Tiaden AN,Kyburz Ddoi
10.1186/s13075-017-1447-1subject
Has Abstractpub_date
2017-11-02 00:00:00pages
245issue
1eissn
1478-6354issn
1478-6362pii
10.1186/s13075-017-1447-1journal_volume
19pub_type
杂志文章abstract:INTRODUCTION:Diverse bone pathologies are observed in patients with psoriatic arthritis (PsA). Uncoupling of bone remodeling with disordered osteoclastogenesis has been implicated in the pathogenesis of PsA. The aim of this study was to examine the role of soluble mediators of bone remodeling within the circulation of ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3123
更新日期:2010-01-01 00:00:00
abstract:INTRODUCTION:Genetic susceptibility to complex diseases has been intensively studied during the last decade, yet only signals with small effect have been found leaving open the possibility that subgroups within complex traits show stronger association signals. In rheumatoid arthritis (RA), autoantibody production serve...
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journal_title:Arthritis research & therapy
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journal_title:Arthritis research & therapy
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更新日期:2009-01-01 00:00:00
abstract:INTRODUCTION:Methotrexate (MTX) is a cornerstone of treatment in a wide variety of inflammatory conditions, including juvenile idiopathic arthritis (JIA) and juvenile dermatomyositis (JDM). However, owing to its narrow therapeutic index and the considerable interpatient variability in clinical response, monitoring of a...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
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journal_title:Arthritis research & therapy
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doi:10.1186/s13075-015-0798-8
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2936
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journal_title:Arthritis research & therapy
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doi:10.1186/ar2817
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journal_title:Arthritis research & therapy
pub_type: 杂志文章,meta分析,评审
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journal_title:Arthritis research & therapy
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
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更新日期:2013-11-06 00:00:00
abstract::Memory T cells display phenotypic heterogeneity. Surface antigens previously regarded as exclusive markers of naive T cells, such as L-selectin (CD62L), can also be detected on some memory T cells. Moreover, a fraction of CD45RO+ (positive for the short human isoform of CD45) memory T cells reverts to the CD45RA+ (pos...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
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更新日期:2003-01-01 00:00:00
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pub_type: 杂志文章
doi:10.1186/ar4417
更新日期:2013-01-01 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4465
更新日期:2014-01-31 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2298
更新日期:2007-01-01 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02276-y
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journal_title:Arthritis research & therapy
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journal_title:Arthritis research & therapy
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar1458
更新日期:2005-01-01 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
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更新日期:2005-01-01 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
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更新日期:2007-01-01 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
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更新日期:2011-01-01 00:00:00
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pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
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