MicroRNA-155 as a proinflammatory regulator via SHIP-1 down-regulation in acute gouty arthritis
© Jin et al.; licensee BioMed Central Ltd. 2014
Received: 5 July 2013
Accepted: 25 March 2014
Published: 7 April 2014
Gout is characterized by episodes of intense joint inflammation in response to intra-articular monosodium urate monohydrate (MSU) crystals. miR-155 is crucial for the proinflammatory activation of human myeloid cells and antigen-driven inflammatory arthritis. The functional role of miR-155 in acute gouty arthritis has not been defined. Therefore, the aim of this study was to examine the role of miR-155 in pathogenesis of acute gouty arthritis.
Samples from 14 patients with acute gouty arthritis and 10 healthy controls (HCs) were obtained. Peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) were cultured in vitro with MSU crystals, and gene expression (human miR-155 and SHIP-1) were assessed by real-time PCR. THP-1 cells were stimulated by MSU crystals and/or miR-155 transfection and then subjected to Western blot analysis. Levels of human tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-1β in cell culture supernatants were measured by Luminex. Immunohistochemistry was performed on formalin-fixed gout tissues with anti–SHIP-1 antibody. A C57BL/6 J male mouse model of gout was used to analyze the expressions of miR-155, SHIP-1, and inflammatory cytokines.
The samples from gouty arthritis were highly enriched in miR-155, with levels of expression being higher than those found in PBMC from HC. Treatment of the cells with MSU crystals strongly induced miR-155. In addition, overexpression of miR-155 in the cells decreased levels of SHIP-1 and promoted production of MSU-induced proinflammatory cytokines, such as TNF-α and IL-1β. Consistent with in vitro observations, miR-155 expression was elevated in the mouse model of gout. The production of inflammatory cytokines was markedly increased in MSU crystal induced peritonitis mice.
Overexpression of miR-155 in the gouty SFMC leads to suppress SHIP-1 levels and enhance proinflammatory cytokines.
Gout is characterized by episodes of intense joint inflammation, in response tointra-articular monosodium urate monohydrate (MSU) crystals . This inflammatory response is specifically initiated by inflammasome activation within monocytes/macrophages, causing activation of inflammatory cytokines within the joint .
miRNA are noncoding RNA oligonucleotides that have been highly conserved during evolution and which have recently emerged as potent regulators of gene expression of posttranscriptional regulators . miRNA have been identified that appear to be critical for fine-tuning many biological processes, and offers the prospect of multiple targets [4, 5]. Emerging data suggest that single miRNA species can profoundly alter the phenotype and outcome of immune responses [6–8].
miR-155 is crucial for the proinflammatory activation of human myeloid cells and antigen-driven inflammatory arthritis . Peripheral blood mononuclear cells (PBMC) in rheumatoid arthritis (RA) express elevated levels of miR-155, which is particularly associated with disease activity . Also, miR-155 is up-regulated in the synovial membrane of RA . miR-155 has a dual effect on the control of autoimmune-triggered destructive arthritis. miR-155 deficiency inhibits the generation of pathogenic self-reactive T and B cell responses. On the other hand, miR-155 controls the development of local bone destruction . The functional role of miR-155 in gouty arthritis has not been defined. Therefore, the aim of this study was to examine the role of miR-155 in the pathogenesis of acute gouty arthritis.
Clinical and laboratory characteristics of patients with gouty arthritis and healthy controls
Age, mean (range) years*
51 (25 to 65)
55 (31 to 68)
Male, number (%)*
Duration of acute gout, mean (range) days
2 (1 to 4)
Diabetes, number (%)
Hypertension, number (%)
Hypercholesterolemia, number (%)
Cardiovascular disease, number (%)
Naive, number (%)
Location of arthritis
First MTP joint, number (%)
Knee joint, number (%)
Ankle joint, number (%)
Serum urate level, mean (range) mg/dl
7 (5 to 12)
ESR, mean (range, mm/h)
55 (45 to 61)
CRP, mean (range, mg/dL)
12.5 (5.8 to 18.3)
MSU crystal synthesis
MSU crystals were prepared by recrystallization from uric acid as previously described . Briefly, 0.4 mg of uric acid was dissolved in 80 ml of boiling distilled water containing 2.45 ml of 1 N NaOH. After adjusting the pH of the solution to 7.2 with HCl, the solution was gradually cooled by stirring at room temperature and stored overnight at 4°C. The crystals that formed were sterilized by heating at 180°C for 2 h and suspended in PBS at a concentration of 1 mg/ml. The crystals obtained by this method were of comparable size (5 to 25 μm long) and needle-shaped, negatively birefringent crystals observed by compensated polarized light microscopy. Endotoxin levels in MSU crystal preparations, as assessed by Limulus amoebocyte cell lysate assay (Lonza, Walkersville, MD, USA), were less than 0.01 IU/ml.
Isolation of PBMCs and synovial fluid mononuclear cells (SFMCs), and MSU stimulation
Peripheral venous blood and synovial fluid samples were collected in heparin-containing tubes. PBMCs and SFMCs were isolated by density-gradient centrifugation using Ficoll-Paque Plus solution (Amersham Biosciences, Uppsala, Sweden). Freshly isolated PBMCs were suspended in a complete medium, consisting of RPMI 1640, 2 mM L-glutamine, 100 units/ml of penicillin, and 100 μg/ml of streptomycin, supplemented with 10% FBS (Gibco BRL, Grand Island, NY, USA), and then plated on 6-cm dishes at a density of 5 × 105 cells/ml. After MSU crystals were added directly to the culture plates, cells were cultured in completed media for the indicated times (4, 12, 24, and 48 h) at 37°C in a 5% CO2 humidified incubator for evaluation of miR-155 and Src homology 2-containing inositol phosphatase (SHIP)-1 gene level.
Real-time polymerase chain reaction (PCR)
Total RNA was isolated using the miRNeasy kit (Qiagen, Valencia, CA, USA). The miScript Reverse Transcription Kit (Qiagen) was used for cDNA preparation. MiScript primer assay (Qiagen) was used for semiquantitative determination of the expression of human miR-155 (MS00003605). The primer sequences were as follows: for human SHIP-1, 5′-GCC-TAC-ACC-AAG-CAG-AAA-GC-3′ (forward), 5′-GGA-CCG-TTC-TTG-GAG-ACA-AA-3′ (reverse). The expression of U6B snRNA or β-actin was used as an endogenous control. A threshold cycle (CT) was observed in the exponential phase of amplification, and quantification of relative expression levels was performed using standard curves for target genes and the endogenous control. Geometric means were used to calculate the ΔΔCT (delta-delta CT) values and are expressed as 2-ΔΔCT. The value of each control sample was set at 1 and was used to calculate the fold-change of the target genes.
Cell culture and stimulation
Freshly isolated PBMCs were cultured in RPMI 1640 containing 10% FBS with macrophage colony-stimulating factor (M-CSF; 30 ng/ml; PeproTech, London, UK). After 7 days, adherent cells were used as macrophages . The acute human monocytic leukaemia THP-1 cell line (TIB-202; American Type Culture Collection, Manassas, VA, USA) was used in a well-characterized model of acute gout . THP-1 cells were seeded on 6-cm dishes at a density of 5 × 105 cells/ml: 50nM miR-155 (UUAAUGCUAAUCGUGAUAGGGGU) or 50 nM scramble control (CCUACGCCACCAAUUUCGU) was mixed with Lipofectamine 2000 reagent (Invitrogen, Carlsbad, CA, USA) in serum-free RPMI and transfected into the cells per the manufacturer’s protocol. Optimal miR-155 expression was confirmed at 24 h post-transfection by the qPCR analysis (See Additional file 1). After transfection, cells were treated with phorbol 12-myristate 13-acetate/ionomycin (PMA; 100 ng/ml) for 3 h to detect the levels of inflammatory cytokines. This treatment increases the phagocytic properties of the cells and induces a constitutive production of proinflammatory cytokines . After PMA stimulation, cells were washed and then stimulated with MSU (100 ug/ml) for 24 h, as described . Human TNF-α and IL-1β levels in cell culture supernatants were measured using Luminex (Millipore, Billerica, MA, USA) according to the instructions of the manufacturer.
Western blot analysis
Cells were harvested after washing with ice-cold PBS and then lysed in extraction buffer (50 mM Tris/HCl (pH 7.5), 150 mM NaCl, 2 mM EDTA, 1% Triton X-100, 1% sodium deoxycholate, 0.1% sodium dodecyl sulfate (SDS) and 0.01% protease inhibitor cocktail). Whole-cell lysates were subjected to 10% SDS- PAGE and western blot analysis. Primary antibodies included anti-actin (Sigma-Aldrich, St Louis, MO, USA), anti-SHIP-1, anti-phospho-Akt, anti-Akt and anti-IκB-α (Cell Signaling Technology, Beverly, MA, USA) antibodies, and horseradish peroxidase (HRP)-conjugated secondary antibodies (Amersham Biosciences, Pittsburgh, PA, USA) were used and blots were developed with enhanced chemiluminescence (ECL) solution (Millipore Corporation, Billerica, MA, USA). Signals were detected and analyzed using an LAS3000 luminescent image analyzer (Fuji Photo Film, Tokyo, Japan) (See Additional file 2).
The gout and osteoarthritis specimens were fixed in 4% paraformaldehyde. The paraffin sections were immunohistochemically stained using LSAB2 system-HRP kit (DakoCytomation, Carpinteria, CA, USA), according to the manufacturer’s instruction. In brief, the sections were deparaffinized, hydrated, and placed in peroxidase block solution for 10 minute. After washing three times in PBS, the sections were incubated with monoclonal mouse SHIP-1 antibody (1:400, Santa Cruz Biotechnology, Santa Cruz, CA, USA) for 2 h, treated with biotinylated link solution for 20 minutes, and streptavidin-HRP solution applied for 20 minutes. For the negative control, primary antiserum was replaced with PBS. Consequently the sections were treated with 3,3-diaminobenzidine (DAB) substrate-chromogen solution for 10 minutes and counterstained with Harris hematoxylin. Images were photographed on a light microscope (Leica, Wetzlar, Germany).
In vivo mouse peritonitis model
Male C57BL/6 J mice used for the experiments were aged 8 to 10 weeks. Peritonitis was induced by intra-peritoneal injection of 3 mg MSU crystals in 250 μl PBS . After 24 h, mice were killed by CO2 exposure and peritoneal cavities were washed with 4 ml of PBS containing 25 units/ml heparin. The cells were collected by peritoneal lavage and analyzed for the expressions of miR-155 (MS00001701), inflammatory cytokines by real-time PCR, and anti-mouse SHIP-1 (Santa Cruz Biotechnology) antibody was used for western blot. The sequences of the primers used were as follows: for glyceraldehydes-3-phosphate dehydrogenase (GAPDH), 5′-TGA-CCA-CAG-TCC-ATG-CCA-TCA-CTG-3′ (forward), 5′-CAG-GAG-ACA-ACC-TGG-TCC-TCA-GTG-3′ (reverse); for IL-1β, 5′- CTC-GTG-CTG-TCG-GAC-CCA-TAT-GAG-3′ (forward), 5′-TGT-ACC-AGT-TGG-GGA-ACT-CTG-CAG-3′ (reverse); for TNF-α, 5′-GGC-TCC-AGG-CGG-TGC-TTG-3′ (forward), 5′- GGG-CTA-CAG-GCT-TGT-CAC-TCG -3′ (reverse).
The Mann–Whitney U-test was performed for continuous variables that were not normally distributed, and chi-square tests were used for categorical variables. The Kruskal-Wallis test was used for the comparison of cytokines among groups. Dunn’s test was used post-hoc to compare all pairs of groups. A P- value <0.05 was considered statistically significant. All statistical analyses were performed using SPSS version 17.0 software (SPSS, Chicago, IL, USA).
Increased expression levels of miR-155 in SFMCs of gouty arthritis patients
Decreased expression levels of SHIP-1 in SFMCs of gouty arthritis patients
MiR-155 promotes the production of pro-inflammatory cytokines
Contribution of miR-155 expression in the mouse model of gout
Emerging data suggest that single miRNA species can profoundly alter the phenotype and outcome of immune responses. Dysregulation of miRNA levels has been reported in a number of pathologic conditions . More than 100 miRNAs are expressed by cells of the immune system, and they have the potential to broadly influence the molecular pathways that control the development and function of immune responses . Of those, miR-155 has been implicated in the differentiation and activation of cells of both the adaptive and the innate immune systems . Expression of miR-155 has been demonstrated in the context of several autoimmune diseases, including RA. Up-regulated expression of miR-155 in PBMC and synovial membrane cells of RA patients has been observed [10, 11]. miR-155 can be induced in macrophages in response to both bacterial and viral-derived antigens that activate Toll-like receptors (TLRs) [21, 22].
Gout is an autoinflammatory disorder associated with deposition of MSU crystals in joints and peri-articular tissues. Reported advances suggest that the innate immune system drives the gouty inflammatory response to MSU . However, given the redundant and highly cell-specific effects mediated by miRNAs species, the precise functional implications of miR-155 expression in the pathogenesis of gouty arthritis have remained obscure.
In this study, miR-155 was up-regulated in SFMCs from patients with gouty arthritis. Furthermore, our in vitro experiments showed that MSU crystals induced increased levels of miR-155. miRNA controls gene expression by targeting mRNA and triggering either translation repression or RNA degradation . Therefore, the prospect of targeting multiple pathways simultaneously is attractive to optimize the neutralization of complex effector immune pathways. Given the evidence for direct interaction between miR-155 and SHIP-1 [17–19], we explored SHIP-1 in the present study. This molecule also has been reported to be a target of miR-155 in the human RA monocyte . In our data, lower expressions of SHIP-1 from gouty SFMC were observed, comparing to those from HC. In vitro, SHIP-1 level was gradually decreased by MSU crystal-mediated stimulation. Interestingly, our histological observation also revealed that the expressions of SHIP-1 in acute gout samples were fewer than those in OA samples. In addition, SHIP-1 proteins were markedly reduced according to enhancing miR-155 level in monocytes. Thus, our data demonstrate that overexpression of miR-155 contribute to down-regulation of SHIP-1 in gouty SFMC.
Cells that encounter MSU crystals express a broad array of inflammatory mediators that contribute to acute gouty inflammation . The role of SHIP-1 is essential for the suppressor activity of macrophages and is a potent inhibitor of many inflammatory pathways [24, 25]. Recently, it has been shown that monocytes and macrophages overexpressing miR-155 exhibit decreased SHIP-1 expression that may lead to increased production of pro-inflammatory cytokines . It can be assumed that the miR-155/SHIP pathway might be responsible for causing excessive pro-inflammatory activation in gouty arthritis. In our cellular biochemical results, a trend (P-value not significant) towards increasing levels of phosphatidylinositol triphosphate (PtdIns-3,4,5-P3) was observed after miR-155 transfection and MSU crystal stimulation (see Additional file 3). Although it appeared that MSU crystal increased PtdIns-3,4,5-P3 levels, this effect was not significantly amplified in the presence of miR-155. The rapid rise and transient accumulation are the main characteristics of PtdIns-3,4,5-P3. Therefore, the possible reason was due to the difficulties of the measurements. Even though the accuracy and sensitivity of the assay for phosphoinositides have been improved, tissue extracts contain large quantities of lipids other than the phosphoinositides, which might be expected to interfere nonspecifically. Among the downstream molecules of PtdIns-3,4,5-P3, Akt is known to phosphorylate IκB kinase (IKK) thereby promoting activation of NF-kB, which is a key factor for inflammatory cytokines . Therefore, in our study, miR-155 decreased the SHIP-1 level, the levels of phosphorylation of Akt were increased, and as a probable consequence, the NF-kB pathway was activated.
With respect to inflammatory cytokines, our in vitro experiments demonstrate that MSU crystals trigger the production of TNF-α in supernatants from stimulated monocytes. Furthermore, miR-155 promoted MSU crystal-induced TNF-α production. Although we could not confirm the increased level of IL-1β induced by miR-155 alone, miR-155 aided IL-1β production in supernatants from MSU crystal-stimulated monocytes. In particular, the elevated levels of pro-inflammatory cytokines, such as IL-1β and TNF-α, in the synovial fluid of patients with gout [27, 28], may be associated with miR-155-mediated regulation of monocyte/macrophage responses to MSU crystals. Taken together, these findings indicate that the pro-inflammatory phenotype in acute gouty arthritis could be regulated by aberrant expression of miR-155. Our in vivo data demonstrated that increased miR-155 expression following stimulation with MSU stimulation plays a role in down-regulation of SHIP-1 protein. Consistent with a crucial role of miR-155 in the regulation of pro-inflammatory cytokine production in vitro, investigations from gout mice model showed that the pro-inflammatory cytokine levels were enhanced in accordance with decreasing levels of SHIP-1.
We have to consider whether miR-155 enhanced proinflammatory cytokines via other pathways, in addition to SHIP-1 signaling on monocytes. It was demonstrated that Akt was directly activated through miR-155–mediated suppression of the phosphatase protein phosphatase 2A catalytic subunit alpha . Jiang et al. demonstrated that miR-155 expression was inversely correlated with the Suppressor of cytokine signaling 1 (SOCS1) gene, that normally functions as a negative feedback regulator of Janus-activated kinase (JAK)/signal transducer, and activator of transcription (STAT) signaling . A recent report also revealed that miR-155 may contribute to experimental autoimmune encephalomyelitis, by promoting the development of inflammatory T cells . Further research on both direct and indirect effects of miR-155 on inflammation by the MSU crystal stimulation are required.
In summary, this study is the first research to examine the role of mirRNA in acute gouty arthritis. miR-155 was up-regulated in SFMCs of patients with gouty arthritis. The pro-inflammatory phenotype in acute gouty arthritis could be regulated by aberrant expression of miR-155. These data provide a strong proof-of-concept for miR-155-based therapeutic approaches that could modulate inflammation in acute gout.
The miR-155 was up-regulated in SFMCs from patients with acute gouty arthritis. The increased expression of miR-155 in SFMCs was associated with lower expression of SHIP-1, an inhibitor of inflammation. Overexpression of miR-155 in SFMC led to down-regulation of SHIP-1. Then Akt/NF-kB pathway was activated, and as a consequence, the production of pro-inflammatory cytokines was enhanced.
erythrocyte sedimentation rate
Nuclear factor of kappa light chain enhancer of B-cells inhibitor
Nuclear factor kappa light chain enhancer of activated B cells
peripheral blood mononuclear cell
standard error of mean
synovial fluid mononuclear cell
Src homology 2-containing inositol phosphatase
Suppressor of cytokine signaling
Signal transducer and activator of transcription
tumor necrosis factor.
This study was supported by grants from the National Research Foundation of Korea (NRF) Grant funded by the Ministry of Education, Science, and Technology (grant number 2011–0008867, 2011–0011332, and 2013R1A2A2A01067956), by the Chonnam National University Hospital Research Institute of Clinical Medicine (grant no. CRI 13008–1), and by Chonnam National University 2011.
- Martinon F, Glimcher LH: Gout: new insights into an old disease. J Clin Invest. 2006, 116: 2073-2075. 10.1172/JCI29404.PubMed CentralView ArticlePubMedGoogle Scholar
- Martinon F, Petrilli V, Mayor A, Tardivel A, Tschopp J: Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature. 2006, 440: 237-241. 10.1038/nature04516.View ArticlePubMedGoogle Scholar
- Bartel DP: MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004, 116: 281-297. 10.1016/S0092-8674(04)00045-5.View ArticlePubMedGoogle Scholar
- O’Connell RM, Rao DS, Chaudhuri AA, Baltimore D: Physiological and pathological roles for microRNAs in the immune system. Nat Rev Immunol. 2010, 10: 111-122. 10.1038/nri2708.View ArticlePubMedGoogle Scholar
- Pillai RS, Bhattacharyya SN, Filipowicz W: Repression of protein synthesis by miRNAs: how many mechanisms?. Trends Cell Biol. 2007, 17: 118-126. 10.1016/j.tcb.2006.12.007.View ArticlePubMedGoogle Scholar
- Xiao C, Srinivasan L, Calado DP, Patterson HC, Zhang B, Wang J, Henderson JM, Kutok JL, Rajewsky K: Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes. Nat Immunol. 2008, 9: 405-414. 10.1038/ni1575.PubMed CentralView ArticlePubMedGoogle Scholar
- Thai TH, Calado DP, Casola S, Ansel KM, Xiao C, Xue Y, Murphy A, Frendewey D, Valenzuela D, Kutok JL, Schmidt-Supprian M, Rajewsky N, Yancopoulos G, Rao A, Rajewsky K: Regulation of the germinal center response by microRNA-155. Science. 2007, 316: 604-608. 10.1126/science.1141229.View ArticlePubMedGoogle Scholar
- Rodriguez A, Vigorito E, Clare S, Warren MV, Couttet P, Soond DR, van Dongen S, Grocock RJ, Das PP, Miska EA, Vetrie D, Okkenhaug K, Enright AJ, Dougan G, Turner M, Bradley A: Requirement of bic/microRNA-155 for normal immune function. Science. 2007, 316: 608-611. 10.1126/science.1139253.PubMed CentralView ArticlePubMedGoogle Scholar
- Kurowska-Stolarska M, Alivernini S, Ballantine LE, Asquith DL, Millar NL, Gilchrist DS, Reilly J, Ierna M, Fraser AR, Stolarski B, McSharry C, Hueber AJ, Baxter D, Hunter J, Gay S, Liew FY, McInnes IB: MicroRNA-155 as a proinflammatory regulator in clinical and experimental arthritis. Proc Natl Acad Sci U S A. 2011, 108: 11193-11198. 10.1073/pnas.1019536108.PubMed CentralView ArticlePubMedGoogle Scholar
- Pauley KM, Satoh M, Chan AL, Bubb MR, Reeves WH, Chan EK: Upregulated miR-146a expression in peripheral blood mononuclear cells from rheumatoid arthritis patients. Arthritis Res Ther. 2008, 10: R101-10.1186/ar2493.PubMed CentralView ArticlePubMedGoogle Scholar
- Stanczyk J, Pedrioli DM, Brentano F, Sanchez-Pernaute O, Kolling C, Gay RE, Detmar M, Gay S, Kyburz D: Altered expression of MicroRNA in synovial fibroblasts and synovial tissue in rheumatoid arthritis. Arthritis Rheum. 2008, 58: 1001-1009. 10.1002/art.23386.View ArticlePubMedGoogle Scholar
- Bluml S, Bonelli M, Niederreiter B, Puchner A, Mayr G, Hayer S, Koenders MI, van den Berg WB, Smolen J, Redlich K: Essential role of microRNA-155 in the pathogenesis of autoimmune arthritis in mice. Arthritis Rheum. 2011, 63: 1281-1288. 10.1002/art.30281.View ArticlePubMedGoogle Scholar
- Murakami Y, Akahoshi T, Hayashi I, Endo H, Kawai S, Inoue M, Kondo H, Kitasato H: Induction of triggering receptor expressed on myeloid cells 1 in murine resident peritoneal macrophages by monosodium urate monohydrate crystals. Arthritis Rheum. 2006, 54: 455-462. 10.1002/art.21633.View ArticlePubMedGoogle Scholar
- Pilling D, Fan T, Huang D, Kaul B, Gomer RH: Identification of markers that distinguish monocyte-derived fibrocytes from monocytes, macrophages, and fibroblasts. PLoS One. 2009, 4: e7475-10.1371/journal.pone.0007475.PubMed CentralView ArticlePubMedGoogle Scholar
- Martinon F, Burns K, Tschopp J: The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol Cell. 2002, 10: 417-426. 10.1016/S1097-2765(02)00599-3.View ArticlePubMedGoogle Scholar
- Getting SJ, Flower RJ, Parente L, de Medicis R, Lussier A, Woliztky BA, Martins MA, Perretti M: Molecular determinants of monosodium urate crystal-induced murine peritonitis: a role for endogenous mast cells and a distinct requirement for endothelial-derived selectins. J Pharmacol Exp Ther. 1997, 283: 123-130.PubMedGoogle Scholar
- O’Connell RM, Chaudhuri AA, Rao DS, Baltimore D: Inositol phosphatase SHIP1 is a primary target of miR-155. Proc Natl Acad Sci U S A. 2009, 106: 7113-7118. 10.1073/pnas.0902636106.PubMed CentralView ArticlePubMedGoogle Scholar
- Cremer TJ, Ravneberg DH, Clay CD, Piper-Hunter MG, Marsh CB, Elton TS, Gunn JS, Amer A, Kanneganti TD, Schlesinger LS, Butchar JP, Tridandapani S: MiR-155 induction by F. novicida but not the virulent F. tularensis results in SHIP down-regulation and enhanced pro-inflammatory cytokine response. PLoS One. 2009, 4: e8508-10.1371/journal.pone.0008508.PubMed CentralView ArticlePubMedGoogle Scholar
- Lee DW, Futami M, Carroll M, Feng Y, Wang Z, Fernandez M, Whichard Z, Chen Y, Kornblau S, Shpall EJ, Bueso-Ramos CE, Corey SJ: Loss of SHIP-1 protein expression in high-risk myelodysplastic syndromes is associated with miR-210 and miR-155. Oncogene. 2012, 31: 4085-4094. 10.1038/onc.2011.579.View ArticlePubMedGoogle Scholar
- di Giovine FS, Malawista SE, Thornton E, Duff GW: Urate crystals stimulate production of tumor necrosis factor alpha from human blood monocytes and synovial cells. Cytokine mRNA and protein kinetics, and cellular distribution. J Clin Invest. 1991, 87: 1375-1381. 10.1172/JCI115142.PubMed CentralView ArticlePubMedGoogle Scholar
- O’Connell RM, Taganov KD, Boldin MP, Cheng G, Baltimore D: MicroRNA-155 is induced during the macrophage inflammatory response. Proc Natl Acad Sci U S A. 2007, 104: 1604-1609. 10.1073/pnas.0610731104.PubMed CentralView ArticlePubMedGoogle Scholar
- Tili E, Michaille JJ, Cimino A, Costinean S, Dumitru CD, Adair B, Fabbri M, Alder H, Liu CG, Calin GA, Croce CM: Modulation of miR-155 and miR-125b levels following lipopolysaccharide/TNF-alpha stimulation and their possible roles in regulating the response to endotoxin shock. J Immunol. 2007, 179: 5082-5089. 10.4049/jimmunol.179.8.5082.View ArticlePubMedGoogle Scholar
- Liu-Bryan R, Scott P, Sydlaske A, Rose DM, Terkeltaub R: Innate immunity conferred by Toll-like receptors 2 and 4 and myeloid differentiation factor 88 expression is pivotal to monosodium urate monohydrate crystal-induced inflammation. Arthritis Rheum. 2005, 52: 2936-2946. 10.1002/art.21238.View ArticlePubMedGoogle Scholar
- Leung WH, Tarasenko T, Bolland S: Differential roles for the inositol phosphatase SHIP in the regulation of macrophages and lymphocytes. Immunol Res. 2009, 43: 243-251. 10.1007/s12026-008-8078-1.PubMed CentralView ArticlePubMedGoogle Scholar
- An H, Xu H, Zhang M, Zhou J, Feng T, Qian C, Qi R, Cao X: Src homology 2 domain-containing inositol-5-phosphatase 1 (SHIP1) negatively regulates TLR4-mediated LPS response primarily through a phosphatase activity- and PI-3 K-independent mechanism. Blood. 2005, 105: 4685-4692. 10.1182/blood-2005-01-0191.View ArticlePubMedGoogle Scholar
- Conde C, Gloire G, Piette J: Enzymatic and non-enzymatic activities of SHIP-1 in signal transduction and cancer. Biochem Pharmacol. 2011, 82: 1320-1334. 10.1016/j.bcp.2011.05.031.View ArticlePubMedGoogle Scholar
- McNearney T, Baethge BA, Cao S, Alam R, Lisse JR, Westlund KN: Excitatory amino acids, TNF-alpha, and chemokine levels in synovial fluids of patients with active arthropathies. Clin Exp Immunol. 2004, 137: 621-627. 10.1111/j.1365-2249.2004.02563.x.PubMed CentralView ArticlePubMedGoogle Scholar
- Chen YH, Hsieh SC, Chen WY, Li KJ, Wu CH, Wu PC, Tsai CY, Yu CL: Spontaneous resolution of acute gouty arthritis is associated with rapid induction of the anti-inflammatory factors TGFbeta1, IL-10 and soluble TNF receptors and the intracellular cytokine negative regulators CIS and SOCS3. Ann Rheum Dis. 2011, 70: 1655-1663. 10.1136/ard.2010.145821.View ArticlePubMedGoogle Scholar
- Bakirtzi K, Hatziapostolou M, Karagiannides I, Polytarchou C, Jaeger S, Iliopoulos D, Pothoulakis C: Neurotensin signaling activates microRNAs-21 and -155 and Akt, promotes tumor growth in mice, and is increased in human colon tumors. Gastroenterology. 2011, 141: 1749-1761. 10.1053/j.gastro.2011.07.038.PubMed CentralView ArticlePubMedGoogle Scholar
- Jiang S, Zhang HW, Lu MH, He XH, Li Y, Gu H, Liu MF, Wang ED: MicroRNA-155 functions as an OncomiR in breast cancer by targeting the suppressor of cytokine signaling 1 gene. Can Res. 2010, 70: 3119-3127. 10.1158/0008-5472.CAN-09-4250.View ArticleGoogle Scholar
- O’Connell RM, Kahn D, Gibson WS, Round JL, Scholz RL, Chaudhuri AA, Kahn ME, Rao DS, Baltimore D: MicroRNA-155 promotes autoimmune inflammation by enhancing inflammatory T cell development. Immunity. 2010, 33: 607-619. 10.1016/j.immuni.2010.09.009.PubMed CentralView ArticlePubMedGoogle Scholar
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