MiR-320a is Downregulated in Patients with Myasthenia Gravis and Modulates Inflammatory Cytokines Production by Targeting Mitogen-activated Protein Kinase 1
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Myasthenia gravis (MG) are T-cell dependent antibody-mediated autoimmune disorders, microRNAs are important regulators of human autoimmune disease pathogenesis. Here, we investigated the miRNAs expression profiles in MG for the first time and found that miR-320a was significantly downregulated in MG patients compared to normal healthy people. Meanwhile, pro-inflammatory cytokins in MG patients were overexpressed. Furthermore, we identified MAPK1 as a direct target of miR-320a. Downregulation of miR-320a induced the overexpression of pro-inflammatory cytokins through promoting COX-2 expression. This process was modulated by ERK/ NF-κB pathways. Taken together, our findings suggested that miR-320a could play a role in modulation of inflammatory cytokins production.
KeywordsMyasthenia gravis miR-320a MAPK1 cytokine COX-2
Mitogen-activated protein kinase1
Glyceraldehyde 3-phosphate dehydrogenase
Peripheral blood mononuclear cell
This work was supported by Shanghai Science and Technology Commission (No. 10JC1414500) and the Shanghai Committee of Science and Technology [grant 11DZ2260600].
- 2.Yang H, Zhang Y, Wu M, Li J, Zhou W, Li G, et al. Suppression of ongoing experimental autoimmune myasthenia gravis by transfer of RelB-silenced bone marrow dentritic cells is associated with a change from a T helper Th17/Th1 to a Th2 and FoxP3+ regulatory T-cell profile. Inflamm Res. 2010;59:197–205.PubMedCrossRefGoogle Scholar
- 11.Cedeno S, Cifarelli DF, Blasini AM, Paris M, Placeres F, Alonso G, et al. Defective activity of ERK-1 and ERK-2 mitogen-activated protein kinases in peripheral blood T lymphocytes from patients with systemic lupus erythematosus: potential role of altered coupling of Ras guanine nucleotide exchange factor hSos to adapter protein Grb2 in lupus T cells. Clin Immunol. 2003;106:41–9.PubMedCrossRefGoogle Scholar
- 27.Khan AQ, Khan R, Qamar W, Lateef A, Ali F, Tahir M, et al. Caffeic acid attenuates 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced NF-kappaB and COX-2 expression in mouse skin: abrogation of oxidative stress, inflammatory responses and proinflammatory cytokine production. Food Chem Toxicol. 2012;50:175–83.PubMedCrossRefGoogle Scholar