Therapeutic potential of IL-15 in rheumatoid arthritis

Yang, Xiao‐Ke; Xu, Wang‐Dong; Leng, Rui‐Xue; Liang, Yan; Liu, Yanyan; Fang, Xinyu; Feng, Chen-Chen; Li, Rui; Cen, Han; Pan, Hai‐Feng; Ye, Dong‐Qing

doi:10.1016/j.humimm.2015.09.041

Cited by 26 publications

(18 citation statements)

References 75 publications

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“…Relevant functions of this cytokine in established RA covers promotion of TNF-α production, activation of T lymphocytes as well as stimulation of osteoclastogenesis [ 25 ]. It was documented that genetic variants in IL-15 associate with progression of joint destruction in RA [ 26 ], and neutralization of IL-15 improves arthritis in animal models and patients with RA [ 27 ]. Furthermore, the levels of IL-15 has been recently shown to be elevated in patients with early RA, and the concentration of this cytokine was shown to predict severe disease course in patients with early arthritis [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Monocyte-related biomarkers of rheumatoid arthritis development in undifferentiated arthritis patients – a pilot study

Kurowska¹,

Kuca-Warnawin²,

Radzikowska³

et al. 2018

Reumatologia

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ObjectivesEnhanced/disturbed activities of monocytes are crucial for perpetuation and for development of rheumatoid arthritis (RA). Therefore, knowledge about monocyte activities and regulation of molecular pathways operating within monocytes early in the course of RA development may help to predict the progression to the full-blown disease. We aimed to investigate the profile of miRNAs expression in circulating monocytes and monocyte-related cytokines in sera of individuals at undifferentiated arthritis (UA) stage, wich could serve as new biomarkers for RA development.Material and methodsMagnetically sorted monocytes from peripheral blood of 20 UA patients served for total RNA isolation. RNA samples were used for microRNA profiling. Concentrations of CCL3/MIP-1α, M-CSF, CCL2/MCP-1, IL-6, TNF-α and IL-15 in sera of UA patients were measured using ELISA assays. Verification of diagnosis after 4 years of follow-up led to the identification of patients who developed RA (UA→RA patients) and patients who remained still in UA phase (UA → UA patients). Comparisons between patients groups were performed using two-tailed Mann-Whitney U test.ResultsWe identified 50 miRNAs in monocytes with the largest variation of expression across all patients samples. From these selected miRNAs, expression of miR-642b-5p, miR-483-3p, miR-371b-5p were significantly up-regulated and miR-25-3p and miR-378d were significantly down-regulated in UA → RA vs. UA → UA patients. This specific pattern of miRNAs expression in circulating monocytes paralleled elevated IL-15 and M-CSF concentrations in sera of UA patients who progressed to RA.ConclusionsResults of our pilot study indicate that altered activity of monocytes can be detected at early stages of RA. We found new miRNA candidates differentially expressed in peripheral blood monocytes and elevated concentrations of IL-15 and M-CSF involved in monocyte activity and differentiation in patients with UA who subsequently developed RA, in comparison to UA patients who did not progress to RA after 4 years follow-up.

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Section: Discussionmentioning

confidence: 99%

Monocyte-related biomarkers of rheumatoid arthritis development in undifferentiated arthritis patients – a pilot study

Kurowska¹,

Kuca-Warnawin²,

Radzikowska³

et al. 2018

Reumatologia

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“…The activity of monomer [K6T]P8 was also tested in synovial fluids from rheumatoid arthritis patients that normally showed high levels of IL-15, and consequently of TNFα [ 82 ].Both P8 and [K6T]P8 peptides were able to inhibit TNFα secretion, with the latter endowed with greater efficacy [ 79 ]. Very recently, [K6T]P8, labeled with technetium-99m (99mTc), showed metabolic stability in synovial fluids from RA patients, and its bio-distribution pattern in healthy rats suggested a slow renal and hepatic elimination.…”

Section: Peptides and Peptidomimetics As Modulators Of Inflammatiomentioning

confidence: 99%

Peptides as Therapeutic Agents for Inflammatory-Related Diseases

Manna

Natale

Florio

et al. 2018

IJMS

123

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Inflammation is a physiological mechanism used by organisms to defend themselves against infection, restoring homeostasis in damaged tissues. It represents the starting point of several chronic diseases such as asthma, skin disorders, cancer, cardiovascular syndrome, arthritis, and neurological diseases. An increasing number of studies highlight the over-expression of inflammatory molecules such as oxidants, cytokines, chemokines, matrix metalloproteinases, and transcription factors into damaged tissues. The treatment of inflammatory disorders is usually linked to the use of unspecific small molecule drugs that can cause undesired side effects. Recently, many efforts are directed to develop alternative and more selective anti-inflammatory therapies, several of them imply the use of peptides. Indeed, peptides demonstrated as elected lead compounds toward several targets for their high specificity as well as recent and innovative synthetic strategies. Several endogenous peptides identified during inflammatory responses showed anti-inflammatory activities by inhibiting, reducing, and/or modulating the expression and activity of mediators. This review aims to discuss the potentialities and therapeutic use of peptides as anti-inflammatory agents in the treatment of different inflammation-related diseases and to explore the importance of peptide-based therapies.

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“…The action of IL‐15 is mainly based on stimulation of the differentiation and proliferation of T cells and natural killer (NK) cells [Mitani et al, ; Waldmann and Tagaya, ]. In addition, although there is no direct evidence, IL‐15 has been implicated in the pathological bone loss of diseases such as RA and PD [McInnes et al, ; Baslund et al, ; Tymkiw et al, ; Yang et al, ]. Therefore, it is likely that IL‐15 is a putative modulator of osteoclast differentiation.…”

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confidence: 99%

IL‐15 and RANKL Play a Synergistically Important Role in Osteoclastogenesis

Okabe

Kikuchi

Mogi

et al. 2016

J of Cellular Biochemistry

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Interleukin-15 (IL-15), a cytokine secreted by several cell types, has important physiological roles in the activity, proliferation, and viability of immune cells. It has both chemoattractant and proinflammatory properties, and may promote bone destruction. A previous study has shown that IL-15 alone exerts no effect on osteoclastogenesis. Therefore, the current study addressed the synergistic effect of IL-15 on osteoclast formation using RAW264.7 (RAW) cells by co-stimulation with receptor activator of nuclear factor (NF)-κB ligand (RANKL) that has a major role in osteoclastogenesis involving the pathogenesis of rheumatoid arthritis and periodontal disease. Co-stimulation of RAW cells by IL-15 and RANKL significantly increased the gene expression of osteoclast differentiation and osteoclastogenesis markers compared with stimulation by RANKL or IL-15 independently as evaluated by tartrate-resistant acid phosphate-positive cell numbers, the fusion index, a pit formation assay with Alizarin red staining (calcification estimation), and quantitative polymerase chain reaction. Phosphorylation of extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase, p38 mitogen-activated protein kinase, and NF-κB was significantly increased by RANKL and IL-15 (P < 0.05) compared with RANKL alone. In addition, these differentiation activities induced by RANKL and IL-15 were comparatively suppressed by inhibition of ERK, suggesting that this synergistic effect on osteoclastogenesis is mainly mediated by ERK. Taken together, our results demonstrate that IL-15 and RANKL induce osteoclastogenesis synergistically, and IL-15 might play a novel and major role in destructive inflammatory bone diseases. J. Cell. Biochem. 118: 739-747, 2017. © 2016 Wiley Periodicals, Inc.

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Therapeutic potential of IL-15 in rheumatoid arthritis

Cited by 26 publications

References 75 publications

Monocyte-related biomarkers of rheumatoid arthritis development in undifferentiated arthritis patients – a pilot study

Monocyte-related biomarkers of rheumatoid arthritis development in undifferentiated arthritis patients – a pilot study

Peptides as Therapeutic Agents for Inflammatory-Related Diseases

IL‐15 and RANKL Play a Synergistically Important Role in Osteoclastogenesis

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