Synovial cell production of IL-26 induces bone mineralization in spondyloarthritis

Heftdal, Line Dam; Andersen, Thomas T.; Jæhger, Ditte Elisabeth; Woetmann, Anders; Østgård, René; Kenngott, Elisabeth E.; Syrbe, Uta; Sieper, Joachim; Hvid, Malene; Deleuran, Bent; Kragstrup, Tue Wenzel

doi:10.1007/s00109-017-1528-2

Cited by 22 publications

(29 citation statements)

References 29 publications

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“…IL-26 has been also detected in the joints of patients suffering from rheumatoid arthritis (RA) (29) and spondyloarthritis (58). More precisely, IL-26 is expressed by fibroblast-like synoviocytes and, to a lower extent, by CD68 + macrophage-like synoviocytes present in inflamed joints from RA patients.…”

Section: The Il-26 Protein and Signaling Elementsmentioning

confidence: 99%

IL-26, a Cytokine With Roles in Extracellular DNA-Induced Inflammation and Microbial Defense

et al. 2019

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Interleukin 26 (IL-26) is the most recently identified member of the IL-20 cytokine subfamily, and is a novel mediator of inflammation overexpressed in activated or transformed T cells. Novel properties have recently been assigned to IL-26, owing to its non-conventional cationic, and amphipathic features. IL-26 binds to DNA released from damaged cells and, as a carrier molecule for extracellular DNA, links DNA to inflammation. This observation suggests that IL-26 may act both as a driver and an effector of inflammation, leading to the establishment of a deleterious amplification loop and, ultimately, sustained inflammation. Thus, IL-26 emerges as an important mediator in local immunity/inflammation. The dysregulated expression and extracellular DNA carrier capacity of IL-26 may have profound consequences for the chronicity of inflammation. IL-26 also exhibits direct antimicrobial properties. This review summarizes recent advances on the biology of IL-26 and discusses its roles as a novel kinocidin.

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Section: The Il-26 Protein and Signaling Elementsmentioning

confidence: 99%

IL-26, a Cytokine With Roles in Extracellular DNA-Induced Inflammation and Microbial Defense

et al. 2019

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“…mineralization in joint tissue from patients with the chronic inflammatory disease spondyloarthritis (8).…”

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confidence: 99%

Interleukin-26 Production in Human Primary Bronchial Epithelial Cells in Response to Viral Stimulation: Modulation by Th17 cytokines

Fru

Kaarteenaho

Lappi‐Blanco

et al. 2017

Mol Med

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Interleukin (IL)-26 is abundant in human airways and this cytokine is involved in the local immune response to a bacterial stimulus in vivo. Specifically, local exposure to the toll-like receptor (TLR) 4 agonist endotoxin does increase IL-26 in human airways and this cytokine potentiates chemotactic responses in human neutrophils. In addition to T-helper (Th) 17 cells, alveolar macrophages can produce IL-26, but it remains unknown whether this cytokine can also be produced in the airway mucosa per se in response to a viral stimulus. Here, we evaluated whether this is the case using primary bronchial epithelial cells from the airway epithelium in vitro and explored the signaling mechanisms involved, including the modulatory effects of additional Th17 cytokines. Finally, we assessed IL-26 and its archetype signaling responses in healthy human airways in vivo. We found increased transcription and release of IL-26 protein after stimulation with the viral-related double stranded (ds) RNA polyinosinic-polycytidylic acid (poly-IC) and showed that this IL-26 release involved mitogen-activated protein (MAP) kinases and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). The release of IL-26 in response to a viral stimulus was modulated by additional Th17 cytokines. Moreover, there was transcription of IL26 mRNA and expression of the protein in epithelial cells of bronchial brush and tissue biopsies respectively after harvest in vivo. In addition, the extracellular IL-26 protein concentrations in bronchoalveolar lavage (BAL) samples did correlate with increased epithelial cell transcription of an archetype intracellular signaling molecule downstream of the IL-26-receptor complex, STAT1, in the bronchial brush biopsies. Thus, our study suggests that viral stimulation causes the production of IL-26 in lining epithelial cells of human airways, structural cells that constitute a critical immune barrier and that this production is modulated by Th17 cytokines.

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“…By contrast, SW982 cell migration rate was low when the cells were connected with BMSC, suggesting that BMSC might produce less chemokines than RAW264.7 cells did. Although synovial cells were implicated to have the ability to induce bone mineralization through production of IL-26 or miRNA, [ 29 ] in the co-culture of FLS, RAW264.7 and BMSC, the number of ALP staining-positive cells decreased, but the number of TRAP staining-positive cells increased. Our previous study showed that BMSC and RAW264.7 cell co-culture increased the activity of ALP, but did not affect TRAP activity [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

A microfluidic chip-based co-culture of fibroblast-like synoviocytes with osteoblasts and osteoclasts to test bone erosion and drug evaluation

Deng

Chen

et al. 2018

R. Soc. open sci.

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Targeting fibroblast-like synoviocyte (FLS) migration and invasion-mediated bone erosion is a promising clinical strategy for the treatment of rheumatoid arthritis (RA). Drug sensitivity testing is fundamental to this scheme. We designed a microfluidic chip-based, cell co-cultured platform to mimic RA FLS-mediated bone erosion and perform drug-sensitive assay. Human synovium SW982 cells were cultured in the central channel and migrated to flow through matrigel-coated side channels towards cell culture chamber where RANKL-stimulated osteoclastic RAW264.7 and osteogenic medium (OS)-stimulated bone marrow mesenchymal stem cells (BMSC) were cultured in the microfluidic chip device, mimicking FLS migration and invasion-mediated bone erosion in RA. These SW982 cells showed different migration potentials to osteoclasts and BMSC. The migration of SW982 cells with high expression of cadherin-11 was more potent when SW982 cells were connected with the co-culture of RAW264.7 and BMSC. Simultaneously, in the co-cultured chamber, tartrate-resistant acid phosphatase (TRAP) activity of RANKL-stimulated RAW264.7 cells was enhanced, but alkaline phosphatase (ALP) activity was decreased in comparison with mono-cultured chamber. Furthermore, it was confirmed that celastrol, a positive drug for the treatment of RA, inhibited SW982 cell migration as well as TRAP activity in the cell-cultured microfluidic chips. Thus, the migration and invasion to bone-related cells was reconstituted on the microfluidic model. It may provide an effective anti-RA drug screen model for targeting FLS migration-mediated bone erosion.

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Synovial cell production of IL-26 induces bone mineralization in spondyloarthritis

Cited by 22 publications

References 29 publications

IL-26, a Cytokine With Roles in Extracellular DNA-Induced Inflammation and Microbial Defense

IL-26, a Cytokine With Roles in Extracellular DNA-Induced Inflammation and Microbial Defense

Interleukin-26 Production in Human Primary Bronchial Epithelial Cells in Response to Viral Stimulation: Modulation by Th17 cytokines

A microfluidic chip-based co-culture of fibroblast-like synoviocytes with osteoblasts and osteoclasts to test bone erosion and drug evaluation

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