Table 1 Summary of Selected miRNA Involvement in Allergy and Asthma

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

Up-regulated in allergic airway inflammation

IL-12p35

Hypertrophic gene of human airway smooth muscle cells

GSK3B

Expression and promoter function are repressed by activation of NF-κB signaling, via ligation of TLRs

NF-κB, TLRs

Downregulated by LPS and oscillations in expression after exposure to TNFα

NF-κB

TNFα

Antagonism of miRNA-126 suppresses the effector function of Th2 cells and the development of allergic airway disease

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

Down-regulation of miR-133a contributes to up-regulation of RhoA in bronchial smooth muscle cells

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

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

LPS-induced expression induced in macrophages

IRAK1, TRAF6

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

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

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

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

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

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

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

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

Associated with psoriasis

Negative regulator of neutrophil proliferation and activation

PU.1, C/EBPα, NFI-A

Mef2c, IGFR

Up-regulated upon mast cell activation and regulate the cell cycle of mast cells

PDGF

p27(kip1), c-Kit