Appendix.
Summary of Selected miRNA Involvement in Allergy and Asthma
| miRNA/reference | Function | Transcriptional Regulation | Targets |
|---|---|---|---|
| let-7i1 | Let-7i regulates TLR 4 expression. NF-κB p50-C/EBPβ silencer complex binds to the let-7i promoter following microbial stimulus to repress let-7i expression | Toll-like | |
| miR-212 | Up-regulated in allergic airway inflammation | IL-12p35 | |
| miR-26a3 | Hypertrophic gene of human airway smooth muscle cells | GSK3B | |
| miR-29b4 | Expression and promoter function are repressed by activation of NF-κB signaling, via ligation of TLRs | NF-κB, TLRs | |
| miR-125b5 | Downregulated by LPS and oscillations in expression after exposure to TNFα | NF-κB | TNFα |
| miR-1266 | Antagonism of miRNA-126 suppresses the effector function of Th2 cells and the development of allergic airway disease | ||
| miR-128b7 | Ectopic expression of miR-128b restores glucocorticoid resistance, while a mutation in miR-128b alters the processing of miR-128b. The resultant downregulation of mature miR-128b contributes to glucocorticoid resistance | MLL-AF4 and AF4-MLL | |
| miR-133a8 | Down-regulation of miR-133a contributes to up-regulation of RhoA in bronchial smooth muscle cells | ||
| miR-146a and miR-2239 | Serum miR-146a and miR-223 were significantly reduced in septic patients and might serve as new biomarkers for sepsis with high specificity and sensitivity | ||
| miR-146a10,11 | Inhibits inflammation. Expression induced in macrophages and alveolar/bronchial epithelium following activation of TLR-2, -4, and -5 or exposure to TNFα and IL-β Critical for in vitro monocytic cell-based endotoxin tolerance12 | NF-κB | IRAK1, TRAF6 |
| miR-146b10 | LPS-induced expression induced in macrophages | IRAK1, TRAF6 | |
| miR-14713 | Induced upon stimulation of multiple TLRs and a negative regulator of TLR-associated signaling events in murine macrophages, forming a negative-feedback loop in which TLR stimulation induces miR-147 to prevent excessive inflammatory responses | TLR2, TLR3, and TLR4 | |
| miR-148a, miR-148b, and miR-15214 | A SNP at the 3¢ UTR of HLA-G, an asthma-susceptibility gene, affects the binding of the three miRNAs. An example of gene-by-epigenetics interaction | ||
| miR-15015 | Significantly reduced in plasma samples of sepsis patients and correlated with the level of disease severity. Plasma levels of TNF-α, IL-10, and IL-18 were negatively correlated with the plasma levels of this miRNA. The plasma levels ratio for miR-150/IL-18 can be used for assessing the severity of sepsis | ||
| miR-15016 | Controls c-Myb expression in vivo in a dose-dependent manner over a narrow range of miRNA and c-Myb concentrations and this dramatically affects lymphocyte development and response. C-Myb regulates asthma susceptibility gene, Gata317 | C-myb | |
| miR-15518 | Induced upon T-cell activation and promotes Th1 differentiation when over-expressed in activated CD4+ T cells. Antagonism of miR-155 leads to induction of IFN-γR. A functional miR-155 target site has been identified within the 3' untranslated region of IFN-γRα | IFN-γRα | |
| miR-15519-22 | Required for normal production of isotype-switched, high-affinity IgG1 antibodies in B-cells. Also determines Th1 and Th2 differentiation and is a positive regulator of antigen-induced responses in T-cells | AP-1 | PU.1, c-Maf |
| miR-15519,23,24 | Regulates lung remodeling. Both miR-146a and miR-155 have also been implicated in the development of rheumatoid arthritis, possibly by regulating components of the inflammatory response | ||
| miR-1555,25-27 | Increased expression following activation of the innate immune response. Inhibits inflammatory mediator release and stimulates granulocyte and monocyte proliferation TLR/IL-1 inflammatory pathway as a general target of miR-155. We further demonstrate that miR-155 directly controls the level of TAB2, an important signal transduction molecule. In mature human DCs, miR-155 is part of a negative feedback loop, which down-modulates inflammatory cytokine production in response to microbial stimuli | AP-1 | |
| miR-203 and miR-146a28 | Associated with psoriasis | ||
| miR-22329-31 | Negative regulator of neutrophil proliferation and activation | PU.1, C/EBPα, NFI-A | Mef2c, IGFR |
| MIRNA-221-22232,33 | Up-regulated upon mast cell activation and regulate the cell cycle of mast cells | PDGF | p27(kip1), c-Kit |
Abbreviations: AP-1, activator protein; Bcl, B-cell lymphoma; C/EBP, CCAAT-enhancer binding protein; C-kit, Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog; C-myb, V-myb myeloblastosis viral oncogene homolog (avian); GSK3B, glycogen synthase kinase 3 beta; HLA-G, human leukocyte antigen G; IFN-γRα, interferon-gamma receptor alpha; IGFR, insulin-like growth factor receptor; IRAK, IL-1 receptor activated kinase; LPS, lipopolysaccharide; Maf, musculoaponeurotic fibrosarcoma; Mef, myeloid ELF-1 like factor; miRNA, microRNA; MLL-AF4, myeloid/lymphoid or mixed-lineage leukemia-ALL1-fused gene from chromosome 4; NFI-A, nuclear factor I/A; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; PDGF, platelet-derived growth factor; TLR, Toll-like receptor; TNF-α, tumor necrosis factor-α; TRAF, TNF receptor-associated factor.