Bruton’s Tyrosine Kinase Is Involved in miR-346-Related Regulation of IL-18 Release by Lipopolysaccharide-Activated Rheumatoid Fibroblast-Like Synoviocytes

Alsaleh, Ghada; Suffert, Guillaume; Semaan, Noha; Juncker, Tom; Frenzel, Laurent; Gottenberg, Jacques-Éric; Sibilia, Jean; Pfeffer, Sébastien; Wachsmann, Dominique

doi:10.4049/jimmunol.0801613

Cited by 133 publications

(83 citation statements)

References 41 publications

(35 reference statements)

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“…81 miR-346 is strongly induced by LPS treatment and targets Btk mRNA in the synovial fibroblasts of rheumatoid arthritis patients. 82 Whether miR-346 targets Btk in macrophages needs to be further studied. Finally, IKKa, one of the IkB kinases in the canonical NFkB pathway, has also been confirmed as a miR-223 targets.…”

Section: Mirnas In Regulation Of Tlr and Rig-i Pathways Yk LI And Xy mentioning

confidence: 99%

MicroRNAs in the regulation of TLR and RIG-I pathways

2012

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The innate immune system recognizes invading pathogens through germline-encoded pattern recognition receptors (PRRs), which elicit innate antimicrobial and inflammatory responses and initiate adaptive immunity to control or eliminate infection. Toll-like receptors (TLRs) and retinoic acid-inducible gene I (RIG-I) are the key innate immune PRRs and are tightly regulated by elaborate mechanisms to ensure a beneficial outcome in response to foreign invaders. Although much of the focus in the literature has been on the study of protein regulators of inflammation, microRNAs (miRNAs) have emerged as important controllers of certain features of the inflammatory process. Several miRNAs are induced by TLR and RIG-I activation in myeloid cells and act as feedback regulators of TLR and RIG-I signaling. In this review, we comprehensively discuss the recent understanding of how miRNA networks respond to TLR and RIG-I signaling and their role in the initiation and termination of inflammatory responses. Increasing evidence also indicates that both virus-encoded miRNAs and cellular miRNAs have important functions in viral replication and host anti-viral immunity.

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Section: Mirnas In Regulation Of Tlr and Rig-i Pathways Yk LI And Xy mentioning

confidence: 99%

MicroRNAs in the regulation of TLR and RIG-I pathways

2012

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“…miRNAs are involved in diverse biological processes, including development, cancer, autoimmunity, and so on (15)(16)(17). Dysregulation of miRNAs by several mechanisms has also been described in various disease states, including SLE (18)(19)(20). However, to the best of our knowledge, studies relevant to miRNAs and lupus CD4 + T cell DNA hypomethylation are still lacking.…”

mentioning

confidence: 96%

MicroRNA-21 and MicroRNA-148a Contribute to DNA Hypomethylation in Lupus CD4+ T Cells by Directly and Indirectly Targeting DNA Methyltransferase 1

Pan

Zhu²,

Yuan

et al. 2010

The Journal of Immunology

508

369

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Systemic lupus erythematosus is a complex autoimmune disease caused by genetic and epigenetic alterations. DNA methylation abnormalities play an important role in systemic lupus erythematosus disease processes. MicroRNAs (miRNAs) have been implicated as fine-tuning regulators controlling diverse biological processes at the level of posttranscriptional repression. Dysregulation of miRNAs has been described in various disease states, including human lupus. Whereas previous studies have shown miRNAs can regulate DNA methylation by targeting the DNA methylation machinery, the role of miRNAs in aberrant CD4+ T cell DNA hypomethylation of lupus is unclear. In this study, by using high-throughput microRNA profiling, we identified that two miRNAs (miR-21 and miR-148a) overexpressed in CD4+ T cells from both patients with lupus and lupus-prone MRL/lpr mice, which promote cell hypomethylation by repressing DNA methyltransferase 1 (DNMT1) expression. This in turn leads to the overexpression of autoimmune-associated methylation-sensitive genes, such as CD70 and LFA-1, via promoter demethylation. Further experiments revealed that miR-21 indirectly downregulated DNMT1 expression by targeting an important autoimmune gene, RASGRP1, which mediated the Ras–MAPK pathway upstream of DNMT1; miR-148a directly downregulated DNMT1 expression by targeting the protein coding region of its transcript. Additionally, inhibition of miR-21 and miR-148a expression in CD4+ T cells from patients with lupus could increase DNMT1 expression and attenuate DNA hypomethylation. Together, our data demonstrated a critical functional link between miRNAs and the aberrant DNA hypomethylation in lupus CD4+ T cells and could help to develop new therapeutic approaches.

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“…In particular, miR-223 is up-regulated in CD4+ naïve T lymphocytes of RA patients, and a possible role of this miRNA in the pathogenesis of the disease has been hypothesized [59]. Alsaleh and colleagues [60] studied the overexpression of miR-346 in RA fibroblast-like synoviocytes, showing that miR-346 indirectly regulates the release of the pro-inflammatory cytokine IL-18.…”

Section: Rheumatoid Arthritismentioning

confidence: 99%

MicroRNAs in systemic rheumatic diseases

et al. 2011

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MicroRNAs (miRNAs) are endogenous, non-coding, single-stranded RNAs about 21 nucleotides in length. miRNAs have been shown to regulate gene expression and thus influence a wide range of physiological and pathological processes. Moreover, they are detected in a variety of sources, including tissues, serum, and other body fluids, such as saliva. The role of miRNAs is evident in various malignant and nonmalignant diseases, and there is accumulating evidence also for an important role of miRNAs in systemic rheumatic diseases. Abnormal expression of miRNAs has been reported in autoimmune diseases, mainly in systemic lupus erythematosus and rheumatoid arthritis. miRNAs can be aberrantly expressed even in the different stages of disease progression, allowing miRNAs to be important biomarkers, to help understand the pathogenesis of the disease, and to monitor disease activity and effects of treatment. Different groups have demonstrated a link between miRNA expression and disease activity, as in the case of renal flares in lupus patients. Moreover, miRNAs are emerging as potential targets for new therapeutic strategies of autoimmune disorders. Taken together, recent data demonstrate that miRNAs can influence mechanisms involved in the pathogenesis, relapse, and specific organ involvement of autoimmune diseases. The ultimate goal is the identification of a miRNA target or targets that could be manipulated through specific therapies, aiming at activation or inhibition of specific miRNAs responsible for the development of disease.

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Bruton’s Tyrosine Kinase Is Involved in miR-346-Related Regulation of IL-18 Release by Lipopolysaccharide-Activated Rheumatoid Fibroblast-Like Synoviocytes

Cited by 133 publications

References 41 publications

MicroRNAs in the regulation of TLR and RIG-I pathways

MicroRNAs in the regulation of TLR and RIG-I pathways

MicroRNA-21 and MicroRNA-148a Contribute to DNA Hypomethylation in Lupus CD4+ T Cells by Directly and Indirectly Targeting DNA Methyltransferase 1

MicroRNAs in systemic rheumatic diseases

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