scholarly journals Expression of sterile-α and armadillo motif in rheumatoid arthritis monocytes correlates with TLR2 induced IL-1β and disease activity

Rheumatology ◽  
2021 ◽  
Author(s):  
Ryan S Thwaites ◽  
Sarah Unterberger ◽  
Giselle Chamberlain ◽  
Henry Gray ◽  
Kelsey Jordan ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Negative Regulator ◽  
Potential Contribution ◽  
Toll Like Receptor ◽  
Blood Monocytes ◽  
Peripheral Blood Monocytes ◽  
Pyrin Domain ◽  
Bone Damage ◽  
Receptor Family

Abstract Objective Cartilage and bone damage in rheumatoid arthritis (RA) are associated with elevated IL-1β. The effects of IL-1β can be reduced by biological therapies that target IL-1β or TNFα. However, the mechanisms responsible for increased IL-1β and the effect of anti-TNFα have not been fully elucidated. Recently, sterile-α and armadillo motif-containing protein (SARM) was identified as a negative regulator of toll-like receptor (TLR) induced IL-1β secretion through an interaction with the inflammasome. This study set out to investigate SARM during TLR induced IL-1β secretion in RA peripheral blood monocytes and in patients commencing anti-TNFα treatment. Methods Monocytes were isolated from RA patients and healthy controls; disease activity was measured by DAS28. IL-1β secretion was measured by ELISA following TLR1/2, TLR4 and TLR7/8 stimulation. The mRNA expression of SARM, IL-1β and the components of the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome were measured by quantitative PCR. SARM protein expression was measured by western blotting. Results TLR1/2 activation induced elevated IL-1β in RA monocytes compared with heathy controls (p= 0.0009), which negatively correlated with SARM expression (p = 0.0086). Lower SARM expression also correlated with higher disease activity (p = 0.0246). Additionally, patients responding to anti-TNFα treatment demonstrated a rapid upregulation of SARM, which was not observed in non-responders. Conclusion Together, these data highlight a potential contribution from SARM to RA pathophysiology where decreased SARM may lead to elevated IL-1β associated with RA pathogenesis. Furthermore, the data additionally present a potential mechanism by which TNFα blockade can modify IL-1β secretion.

scholarly journals Enhanced bacterial phagocytosis by peripheral blood monocytes in rheumatoid arthritis.

1984 ◽  
Vol 43 (3) ◽  
pp. 435-439 ◽  
Author(s):  
M M Steven ◽  
S E Lennie ◽  
R D Sturrock ◽  
C G Gemmell
Keyword(s):  
Rheumatoid Arthritis ◽  
Peripheral Blood ◽  
Blood Monocytes ◽  
Peripheral Blood Monocytes

scholarly journals Promotion of osteoclastogenesis by IL-26 in rheumatoid arthritis

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Kyung-Ann Lee ◽  
Kyoung-Woon Kim ◽  
Bo-Mi Kim ◽  
Ji-Yeon Won ◽  
Hong Ki Min ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Peripheral Blood ◽  
Osteoclast Differentiation ◽  
Joint Damage ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tartrate Resistant Acid Phosphatase ◽  
Dependent Manner ◽  
Receptor Subunit ◽  
Blood Monocytes ◽  
Peripheral Blood Monocytes

Abstract Background The inflammatory cascade in the rheumatoid arthritis (RA) synovium is modulated by a variety of cytokine and chemokine networks; however, the roles of IL-26, in RA pathogenesis, are poorly defined. Here, we investigated the functional role of interleukin-26 (IL)-26 in osteoclastogenesis in RA. Methods We analyzed levels of IL-20 receptor subunit A (IL-20RA), CD55, and receptor activator of nuclear factor kappaB (NF-κB) ligand (RANKL) in RA fibroblast-like synoviocytes (FLSs) using confocal microscopy. Recombinant human IL-26-induced RANKL expression in RA-FLSs was examined using real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). Human peripheral blood monocytes were cultured with macrophage colony-stimulating factor (M-CSF) and IL-26, after which osteoclastogenesis was evaluated by counting the number of tartrate-resistant acid phosphatase-positive multinucleated cells. Additionally, osteoclastogenesis was evaluated by monocytes co-cultured with IL-26-prestimulated FLSs. Results The expression of IL-20RA in RA-FLSs was higher than that in osteoarthritis-FLSs. Additionally, in IL-26-pretreated RA-FLSs, the expression of IL-20RA (but not IL-10 receptor subunit B) and RANKL increased in a dose-dependent manner, with IL-26-induced RANKL expression reduced by IL-20RA knockdown. Moreover, IL-26-induced RANKL expression was significantly downregulated by inhibition of signal transducer and activator of transcription 1, mitogen-activated protein kinase, and NF-κB signaling. Furthermore, IL-26 promoted osteoclast differentiation from peripheral blood monocytes in the presence of low dose of RANKL, with IL-26 exerting an additive effect. Furthermore, co-culture of IL-26-pretreated RA-FLSs with peripheral blood monocytes also increased osteoclast differentiation in the absence of addition of RANKL. Conclusions IL-26 regulated osteoclastogenesis in RA through increased RANKL expression in FLSs and direct stimulation of osteoclast differentiation. These results suggest the IL-26/IL-20RA/RANKL axis as a potential therapeutic target for addressing RA-related joint damage.

scholarly journals Proteinase-activated receptor 2 expression on peripheral blood monocytes and T-cells in patients with rheumatoid arthritis

2016 ◽  
Vol 38 (2) ◽  
pp. 91-98 ◽  
Author(s):  
Samia H. Kandel ◽  
Wafaa M. Radwan ◽  
Heba A. Esaily ◽  
Shimaa F. Al-mahmoudy
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Peripheral Blood ◽  
Blood Monocytes ◽  
Peripheral Blood Monocytes

scholarly journals TLR1/2 and 5 induce elevated cytokine levels from rheumatoid arthritis monocytes independent of ACPA or RF autoantibody status

Rheumatology ◽  
2020 ◽  
Vol 59 (11) ◽  
pp. 3533-3539
Author(s):  
Ryan S Thwaites ◽  
Sarah Unterberger ◽  
Giselle Chamberlain ◽  
Karen Walker-Bone ◽  
Kevin A Davies ◽  
...  
Keyword(s):  
Disease Activity ◽  
Progressive Disease ◽  
Disease Activity Score ◽  
Joint Disease ◽  
Blood Monocytes ◽  
Peripheral Blood Monocytes ◽  
Cytokine Levels ◽  
Healthy Control ◽  
Autoantibody Status ◽  
Tlr9 Activation

Abstract Objective RA is an autoimmune inflammatory joint disease. Both RF and ACPA are associated with more progressive disease and higher levels of systemic inflammation. Monocyte activation of toll-like receptors (TLRs) by endogenous ligands is a potential source of increased production of systemic cytokines. RA monocytes have elevated TLRs, some of which are associated with the disease activity score using 28 joints (DAS28). The aim of this study was to measure TLR-induced cytokine production from monocytes, stratified by autoantibody status, to assess if their capacity to induce cytokines is related to autoantibody status or DAS28. Methods Peripheral blood monocytes isolated from RA patients and healthy controls were stimulated with TLR1/2, TLR2/6, TLR4, TLR5, TLR7, TLR8 and TLR9 ligands for 18 h before measuring IL-6, TNFα and IL-10. Serum was used to confirm the autoantibody status. Cytokine levels were compared with RF, ACPA and DAS28. Results RA monocytes demonstrated significantly increased IL-6 and TNFα upon TLR1/2 stimulation and IL-6 and IL-10 upon TLR5 activation. TLR7 and TLR9 activation did not induce cytokines and no significant differences were observed between RA and healthy control monocytes upon TLR2/6, TLR4 or TLR8 activation. When stratified by ACPA or RF status there were no correlations between autoantibody status and elevated cytokine levels. However, TLR1/2-induced IL-6 did correlate with DAS28. Conclusions Elevated TLR-induced cytokines in RA monocytes were not related to ACPA or RF status. However, TLR1/2-induced IL-6 was associated with disease activity.

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