Human Mesenchymal Stem Cells Suppress the Stretch–Induced Inflammatory miR-155 and Cytokines in Bronchial Epithelial Cells

Abstract

Current research in pulmonary pathology has focused on inflammatory reactions initiated by immunological responses to allergens and irritants. In addition to these biochemical stimuli, physical forces also play an important role in regulating the structure, function, and metabolism of the lung. Hyperstretch of lung tissues can contribute to the inflammatory responses in asthma, but the mechanisms of mechanically induced inflammation in the lung remain unclear. Our results demonstrate that excessive stretch increased the secretion of inflammatory cytokines by human bronchial epithelial cells (hBECs), including IL-8. This increase of IL-8 secretion was due to an elevated microRNA-155 (miR-155) expression, which caused the suppression of Src homology 2 domain–containing inositol 5-phosphatase 1 (SHIP1) production and the subsequent activation of JNK signaling. In vivo studies in our asthmatic mouse model also showed such changes in miR-155, IL-8, and SHIP1 expressions that reflect inflammatory responses. Co-culture with human mesenchymal stem cells (hMSCs) reversed the stretch-induced hBEC inflammatory responses as a result of IL-10 secretion by hMSCs to down-regulate miR-155 expression in hBECs. In summary, we have demonstrated that mechanical stretch modulates the homeostasis of the hBEC secretome involving miR-155 and that hMSCs can be used as a potential therapeutic approach to reverse bronchial epithelial inflammation in asthma.

Small interfering RNA directed against microRNA‑155 delivered by a lentiviral vector attenuates asthmatic features in a mouse model of allergic asthma

“…These data indicate that the upregulation of miR-155 is associated with the pathogenesis of asthma. Certain previous studies have revealed that higher miR-155 expression exists in the smooth muscle cells of asthmatic airways (33) and bronchial epithelial cells (34), which is partly consistent with the results of the present study. However, further exploration of the function of miR-155 in other cell types will be important to understand the role of miR-155 in the development of the allergic immune response.…”

MicroRNA regulation of allergic inflammation and asthma

“…Hyperstretch can also contribute to the pathogenesis of obstructive lung diseases, such as allergic asthma. miR-155 is induced by stretch in human bronchial epithelium, contributes to IL-8 secretion, and directly targets the phosphatase SHIP1[46]. Taken together, these studies reinforce the paradigm that miRNAs regulate cell responses and function by inhibiting the expression of target gene networks.…”

Stem Cell Research and Social Justice: Aligning Scientific Progress with Social Need

“…Fortunately, there is no shortage of stem cell research dedicated to the health conditions that disproportionately affect racial and ethnic minorities in the USA, conditions like asthma, heart disease, liver disease, and HIV/ AIDS. For example, mesenchymal stem cells have been explored extensively as a potential treatment for asthma [12][13][14]. In addition, a plethora of research has been conducted on the use of stem cells to understand and treat cardiac damage following heart disease [15][16][17].…”