MiR-320a is Downregulated in Patients with Myasthenia Gravis and Modulates Inflammatory Cytokines Production by Targeting Mitogen-activated Protein Kinase 1

Cheng, Zhuoan; Qiu, Shaobo; Jiang, Lin; Zhang, Anle; Bao, Wenjing; Ping, Liu; Liu, Jianwen

doi:10.1007/s10875-012-9834-5

Cited by 67 publications

(60 citation statements)

References 28 publications

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“…In this study, miR-320a and miR-18a, had significantly altered expression in AMC after MALP-2 treatment compared to untreated controls (Figure 6B). MiR-320a has been shown to directly target MAPK1 in human lymphocytes, and inhibit ERK activity, while up-regulating JNK activity [37]. Thus this may explain the lack of phosphorylated ERK1/2 observed in AMC treated with MALP-2 (data not shown) despite the activation of NF-κB.…”

Section: Discussionmentioning

confidence: 96%

Human amnion mesenchymal cells are pro-inflammatory when activated by the Toll-like receptor 2/6 ligand, macrophage-activating lipoprotein-2

et al. 2016

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Introduction Infection accounts for over 40% of preterm premature rupture of the fetal membranes (PPROM), a major cause of preterm birth. Toll-like receptors (TLR) play key roles in pathogen surveillance but their expression and function in amnion mesenchymal cells (AMC) is unclear. The aims of this study were to determine the expression of all TLR isoforms and the effect of macrophage-activating lipoprotein-2 (MALP-2), derived from a common pathogen involved in PPROM, on human AMC. Methods AMC were isolated from normal, term, amnion from repeat caesarean section. Semi-quantitative RT-PCR, immunocytochemistry, immunohistochemistry and western blotting were used to detect TLR isoform expression. Immunocytochemistry of NF-κB p65, pro-inflammatory cytokine secretion (ELISA), MTT assay, LDH assay, immunoblotting of cytosolic cytochrome c and cleaved caspase-3, and expression of 84 microRNAs by Qiagen miRNA PCR array were used to determine the functional effect of MALP-2 on AMC. Results TLR1-10 was detected in AMC, and protein expression of TLR2, 4, and 6 were confirmed. MALP-2 induced nuclear translocation of p65, reaching significance after 45 minutes (ANOVA, P < 0.05). MALP-2 did not cause apoptosis but did lead to significant secretion of IL-4, IL-6, and IL-8 (P < 0.05, 0.01, 0.001, respectively) and significant changes in miRNA-320a and miRNA-18a (P < 0.05). Discussion These results suggest that AMC elicit a pro-inflammatory response following stimulation with the known TLR2/6 ligand MALP-2. This data supports the idea that AMC express the innate immune system receptors that could help with immune surveillance during infection and contribute to inflammatory responses that lead to PPROM.

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Section: Discussionmentioning

confidence: 96%

Human amnion mesenchymal cells are pro-inflammatory when activated by the Toll-like receptor 2/6 ligand, macrophage-activating lipoprotein-2

et al. 2016

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“…MG is a serial of antibody-mediated autoimmune disorders that are T-celldependent. 20 TNF-α, as a pro-inflammatory cytokine derived from macrophage-monocyte lineage, is involved in driving autoimmunity. 21 TNF blockade has been reported to regulate B-cell responses, particularly inducing T-cell-dependent humoral immunity.…”

Section: Discussionmentioning

confidence: 99%

Correlations of TNF-α gene promoter polymorphisms with the risk of thymoma-associated myasthenia gravis in a northern Chinese Han population

Lei

Xie

et al. 2017

Cancer Gene Ther

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This study was performed with the aim to investigate the correlations of tumor necrosis factor-alpha (TNF-α) gene promoter polymorphisms with the risk of thymoma-associated myasthenia gravis (T-MG) in a northern Chinese Han population. Between June 2005 and June 2015, 305 MG patients (150 males and 155 females, MG group) and 293 healthy volunteers (negative control (NC) group) were enrolled in this study. Among the MG patients, there were 121 patients with thymoma-associated MG (T-MG group) and 184 without T-MG (NT-MG group). Enzyme-linked immunosorbent assay (ELISA) was used for the serum TNF-α level. Polymerase chain reaction-restriction fragment length polymorphism was conducted to determine genotype and allele frequencies of TNF-α gene promoter -1031T/C, -857C/T and -863C/A. The haplotype was analyzed with the SHEsis software. Logistic regression analysis was performed for correlations between TNF-α gene promoter polymorphisms and the risk of T-MG. The T-MG group had higher frequencies of the CT/TT genotype and T allele of -857C/T than the NT-MG and NC groups. The frequencies of the CC genotype and C allele of -1031T/C were higher in the T-MG group than in the NT-MG and NC groups, and higher in male patients in the T-MG group than in male patients in the NC group. TTA and TTC haplotypes exhibited lower frequencies in the T-MG group than in the NT-MG group. The ocular MG patients exhibited lower frequencies of the TT genotype and T allele of -857C/T than the generalized MG patients did. The TNF-α level was elevated in the T-MG group compared with that in the NC and NT-MG groups, indicating that the TC+CC and CT+TT genotypes were increased compared with the TT and CC genotypes in the -1031T/C and -857C/T, respectively. Logistic regression analysis suggested that expressions of anti-acetylcholine receptor antibodies, Osserman's classification, -1031T/C and -857C/T polymorphisms and the TTA haplotype were the independent risk factors for T-MG. These findings reveal that TNF-α -1031T/C and -857C/T polymorphisms and the TTA haplotype may be correlated with the occurrence of T-MG in a Northern Chinese Han population.

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“…Recent data suggest that microRNA (miRNA) could play an important role in modulating the immune response. Cheng et al (2013) described for the first time a list of 34 miRNAs dysregulated in the peripheral blood mononuclear cell from myasthenia gravis patients in a Chinese cohort. The downregulation of miR320 in myasthenia gravis patients is correlated with the increase in proinflammatory cytokine [IL-2, interferon (IFN)-γ, IL-17, IL-6] production.…”

Section: Fig 2 Tslp Protein Expression In Thymoma Cells (A and B)mentioning

confidence: 99%

Aberrant decrease of microRNA19b regulates TSLP expression and contributes to Th17 cells development in myasthenia gravis related thymomas

Wang

Chen

et al. 2015

Journal of Neuroimmunology

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MiR-320a is Downregulated in Patients with Myasthenia Gravis and Modulates Inflammatory Cytokines Production by Targeting Mitogen-activated Protein Kinase 1

Cited by 67 publications

References 28 publications

Human amnion mesenchymal cells are pro-inflammatory when activated by the Toll-like receptor 2/6 ligand, macrophage-activating lipoprotein-2

Human amnion mesenchymal cells are pro-inflammatory when activated by the Toll-like receptor 2/6 ligand, macrophage-activating lipoprotein-2

Correlations of TNF-α gene promoter polymorphisms with the risk of thymoma-associated myasthenia gravis in a northern Chinese Han population

Aberrant decrease of microRNA19b regulates TSLP expression and contributes to Th17 cells development in myasthenia gravis related thymomas

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