Abstract
MicroRNAs (miRNAs) play powerful roles in immune function by regulating target genes that mediate cell behavior. It is well known that mast cells have essential effector and immune regulatory functions in IgE-associated allergic disorders and in innate and adaptive immune responses. However, the role of miRNAs in mediating mast cell functions and the relevant mechanisms require further exploration. The roles of miR-33b in airway inflammation and mast cell functions are still unknown. To examine the role of miR-33b in mouse mast cells in cockroach allergen-induced asthma, we developed a lentiviral system for miRNA-33b overexpression to examine whether miRNA-33b mediates airway inflammation by regulating mast cell function and to evaluate the underlying mechanism. The results showed that miR-33b inhibited cockroach allergen-induced asthma in vivo: in particular, it inhibited TH2 cytokine production. In addition, we found that in cells in which miRNA-33b had been transfected, mast cell degranulation was inhibited through suppression of the calcium release and IgE/FcεRI pathway. Our study provides new insight into the roles of miR-33b in asthma and mast cell biology and identifies novel mechanisms that may contribute to mast cell-related pathological conditions in airway inflammation.
Highlights
Asthma is characterized by airway obstruction and inflammation, mucus overproduction, airway hyper-responsiveness (AHR) and high IgE production in response to environmental factors and allergy[1]
We found that miR-33b expression was highly decreased in the cockroach allergen (CRE)-challenged group compared to the PBS group (Fig. 1A)
The results showed that the levels of degranulation were significantly suppressed in the mast cells that had been transfected with miR33b compared with those treated with miR-NC (Fig. 5A)
Summary
All methods were performed in accordance with the relevant guidelines and regulations of the Central Laboratory at Hunan Provincial People’s Hospital. Decreases in LTC4 secretion (Fig. 5B) and Tinterleukin 13 (IL-13) expression (Fig. 5C) were observed in the miR-33b-treated BMMCs. In vivo, we used a passive cutaneous anaphylaxis (PCA) model to further test the ability of miR-33b to inhibit mast cell activation. The control groups included administration of PBS or naïve BMMCs. To provide further evidence that the miR-33b level affected the mast cell transfer model, we collected lung tissue to examine miR-33b expression. We found that the C57BL/6 mice into which the miR-NC BMMCs had been adoptively transferred exhibited increased numbers of mast cells (Fig. 7C). L and IgG1 compared with those engrafted with miR-NC BMMCs (Fig. 7E–G) These observations indicate that miR-33b in mast cells may inhibit CRE-induced allergic inflammation and asthma in vivo
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