Effects of AntagomiRs on Different Lung Diseases in Human, Cellular, and Animal Models

Murdaca, Giuseppe; Tonacci, Alessandro; Negrini, Simone; Greco, Monica; Borro, Matteo; Puppo, Francesco; Gangemi, Sebastiano

development of DAH, noticing that this molecule targets several pro-inflammatory mediators. The extent of lung inflammation was markedly reduced in miR-155-knockout (miR-1552/2) mice. Moreover, in vivo silencing of miR-155 using miR-155 antagomiR reduced the incidence of iatrogenicinduced DAH. MiR-155 cooperates with Th2 responses too. In fact, it is extensively expressed in the Th cell, DCs, and macrophages in the lung. MiR-155 was also found to be up-regulated in the nasal mucosa and airway smooth muscle cells of allergic asthmatic patients [27, 100, 101] . Recently, Plank et al. [30] conducted a study on murine asthmatic models noticing that MiR-155-5p is highly upregulated in mice. However, while targeting of miR-155-5p with a specific antagomiR resulted in specific inhibition in vivo, it was not able to alter the disease phenotype. Authors hypothesized that this could be due to the variation in antagomiR uptake, which demonstrated to be effective in myeloid cells and weak in lymphocytes. Cystic fibrosis (CF) is an autosomal recessive disease, due to the occurrence of cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations and it is characterized by a variable cytokines pro-inflammatory milieu. Bhattacharyya et al. [29] demonstrated that antagomiR-155 down-regulates miR-155 expression suppressing IL-8 and other proinflammatory genes in CF cells.