MicroRNA-155 as a therapeutic target for inflammatory diseases

Kanwal, Naghmana; John, Peter; Bhatti, Attya

doi:10.1007/s00296-012-2559-1

Cited by 9 publications

(11 citation statements)

References 26 publications

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“…not only confirmed the over‐expression of miRNA‐146a (miR‐146a) in the peripheral mononuclear cells of patients with pSS but demonstrated the unanticipated over‐expression of its functionally coupled gene, TRAF6 , in parallel . The miR‐155 is regarded as a central modulator of T‐cell responses and a potential therapeutic target for certain inflammatory diseases . In the current study we analyzed the expression rate of miR‐155 and its functionally linked gene, the suppressor gene of cytokine signaling 1 ( SOCS1 ), in the peripheral mononuclear cells of patients with pSS and healthy controls.…”

Section: Introductionmentioning

confidence: 71%

“…10 The miR-155 is regarded as a central modulator of T-cell responses 11 and a potential therapeutic target for certain inflammatory diseases. 12,13 In the current study we analyzed the expression rate of miR-155 and its functionally linked gene, the suppressor gene of cytokine signaling 1 (SOCS1), 13 in the peripheral mononuclear cells of patients with pSS and healthy controls.…”

Section: Introductionmentioning

confidence: 99%

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Simultaneously increased expression of microRNA‐155 and suppressor of cytokine signaling 1 (SOCS1) gene in the peripheral blood mononuclear cells of patients with primary Sjögren's syndrome

et al. 2015

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Section: Introductionmentioning

confidence: 71%

Section: Introductionmentioning

confidence: 99%

Simultaneously increased expression of microRNA‐155 and suppressor of cytokine signaling 1 (SOCS1) gene in the peripheral blood mononuclear cells of patients with primary Sjögren's syndrome

et al. 2015

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“…The variable dysregulated expression of miR-155 has been shown in autoimmune diseases such as SLE [44]. miR-155 can be used as a therapeutic target for inflammatory diseases [45]. Deleting miR-155 reduces the autoantibody responses and alleviates lupus-like disease in the Fas(lpr) mouse [46].…”

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confidence: 99%

TLR9‐induced miR‐155 and Ets‐1 decrease expression of CD1d on B cells in SLE

et al. 2015

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B cells present lipid antigens to CD1d-restricted invariant natural killer T (iNKT) cells to maintain autoimmune tolerance, and this process is disrupted in systemic lupus erythematosus (SLE). Inflammation may inhibit CD1d expression to exacerbate the pathology of lupus. However, how inflammation regulates CD1d expression on B cells is unclear in SLE.In the present study, we showed that the surface expression of CD1d on B cells from SLE mice was decreased and that stimulation of inflammatory responses through TLR9 decreased the membrane and total CD1d levels of CD1d on B cells. Moreover, inflammation-related microRNA-155 (miR-155) negatively correlated with the expression of CD1d in B cells. miR-155 directly targeted the 3 -untranslated region (3 -UTR) of CD1d upon TLR9 activation in both humans and mice. The inhibitory effects of miR-155 on CD1d expression in B cells impaired their antigen-presenting capacity to iNKT cells. In addition, Ets-1, a susceptibility gene of SLE, also directly regulated the expression of the CD1d gene at the transcriptional level. These findings provide new insight into the mechanism underlying decreased CD1d expression on B cells in SLE, suggesting that inhibition of inflammation may increase CD1d expression in B cells to ameliorate SLE via modulating iNKT cells.Keywords: B cells r CD1d r Ets-1 r miR-155 r SLE Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionSystemic lupus erythematosus (SLE) is a complex and chronic autoimmune disease with an unclear etiology [1]. B cells play a central role in the pathogenesis of SLE [2], and patients with SLE exhibit abnormal B-cell activation and increased sensitivity and proliferation of B cells [3]. Moreover, the Correspondence: Dr. Yayi Hou e-mail: yayihou@nju.edu.cn clinical success of B-cell depletion therapy further proves the important role of B cells in SLE pathogenesis [4,5]. B cells not only produce antibodies and release cytokines and chemokines but also present both peptide and lipid antigens [6].CD1 family molecules are nonclassical MHC proteins related to the class I MHC proteins and are involved in the presentation of lipid antigens to T cells. Several studies have suggested that CD1d may play an immunoregulatory role in the development of lupus, and CD1d deficiency exacerbates lupus nephritis in the pristineinduced model [7] and inflammatory dermatitis in MRL-lpr/lpr C 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2015. 45: 1934-1945 Cellular immune response 1935 mice [8]. Importantly, endogenous DNA stimulates inflammatory responses through TLR9 and exacerbates lupus disease pathology [9,10]. Viral infection could downregulate the expression of CD1d in APCs, such as B cells [11,12], DCs, and macrophages [13]. A number of exogenous viruses, especially Epstein-Barr virus (EBV) [14,15], also have been linked to the pathogenesis of SLE [16]. Our previous studies have indicated that ligands for both TLR9 and TLR7 lead to B...

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“…Therapeutic strategies incorporating microRNA have been applied in several disease states, including cancer, diabetes, and cardiovascular disease [56,57,58]. miR-155 has also been targeted recently as a therapeutic in inflammatory diseases including rheumatoid arthritis [59]. The strategies fall broadly into two categories: (1) inhibitory anti-sense RNA and (2) exogenous miRNA like molecules [56].…”

Section: Discussionmentioning

confidence: 99%

The Role of MicroRNA-381 in Chondrogenesis and Interleukin-1-β Induced Chondrocyte Responses

Hou

Meng

Zhang

et al. 2015

Cell Physiol Biochem

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Aim: The molecular pathways regulating cartilage degradation are unclear. miR-381 was identified as a putative regulator of chondrogenesis related genes. Here, we examined its role in chondrogenesis and osteoarthritic cartilage degeneration. Methods: miR-381 expression was assessed in vitro in response to IL-1β stimulation in primary human (PHC) and mouse (PMC) chondrocytes, and ATDC5 derived chondrocytes; and in vivo in mouse embryos and human osteoarthritic cartilage. The effects of miR-381 on chondrogenesis and NF-kB signaling were assessed using a synthetic RNA mimic or inhibitor and luciferase assay, respectively. Upstream regulators of miR381 were probed using siRNA or overexpression plasmids for Sox9 and Runx2. Results: miR-381 expression was elevated in chondrogenic and hypertrophic ATDC5 cells. miR-381 was induced in vitro by IL-1β in ATDC5 cells, PMCs, and PHCs, and was expressed in areas of cartilage degradation or absorption in vivo. Overexpression of Runx2 or Sox9 increased miR-381 expression in ATDC5 cells. miR-381 suppressed expression of collagen, type II, alpha 1, and enhanced expression of metalloproteinase-13 (MMP-13), but did not regulate NFKBIA and NKRF activity. Conclusion: miR-381 was highly expressed during chondrogenesis and in arthritic cartilage. It may contribute to absorption of the cartilage matrix by repressing type II collagen and inducing MMP-13.

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MicroRNA-155 as a therapeutic target for inflammatory diseases

Cited by 9 publications

References 26 publications

Simultaneously increased expression of microRNA‐155 and suppressor of cytokine signaling 1 (SOCS1) gene in the peripheral blood mononuclear cells of patients with primary Sjögren's syndrome

Simultaneously increased expression of microRNA‐155 and suppressor of cytokine signaling 1 (SOCS1) gene in the peripheral blood mononuclear cells of patients with primary Sjögren's syndrome

TLR9‐induced miR‐155 and Ets‐1 decrease expression of CD1d on B cells in SLE

The Role of MicroRNA-381 in Chondrogenesis and Interleukin-1-β Induced Chondrocyte Responses

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