Therefore, the downregulation of TGF-β2 protein by miR-141 may be an important step in the excessive inflammation progression during influenza A virus infection, particularly in H5N1 infection. However, whether the recovery of TGF-β2 expression by anti-miR miR-141 inhibitor could resolve the hypercytokinemia learn more stage of H5N1 infection needs to be further studied. Although our findings were obtained from an in vitro model, we could apply these to the real situation of an in vivo model or tissue comprised of different cell types. In real bronchial environments, lung epithelial cells are the key target of influenza viruses [33, 34]. After these cells are infected, they will activate an
inflammatory cascade which launches a quick antimicrobial reaction and directs adaptive immunity to mount a protective response. Bronchial epithelial cells therefore modulate the activation of monocytes, macrophages,
dendritic cells (DC), and T lymphocytes through cytokines and chemokines. Cytokines and chemokines generally function in an autocrine (on the producing cell itself) or paracrine (on nearby cells) manner. These mediators will EPZ015666 chemical structure contribute to the generation of a specific bronchial homeostatic microenvironment that affects the way in which the body copes with the SBI-0206965 viruses. This homeostatic “circuit” can inhibit excessive inflammatory response in lung tissues . For example, TGF-β before had been reported to mediate a cross-talk between alveolar macrophages and epithelial cells . However, our findings show that, during highly pathogenic H5N1 avian virus infection, miR-141 would be induced shortly after infection. With high level of miR-141, the expression of TGF-β would be suppressed from the lung epithelial cells. Without sufficient TGF- β, the pro-inflammatory
response might not be tightly controlled in cases of highly pathogenic H5N1 avian virus infection. This might explain the mechanism concerning bronchial infiltration of inflammatory cells, particularly lymphocytes and eosinophils, and the subsequent hyperresponsiveness of the bronchial wall induced by viral infection. Our study has some limitations that will need to be addressed in future studies. Firstly, we did not assess the roles of other miRNAs whose expression were also altered after infection. The miRNA microarrays that we used did not contain probes for every known miRNA; thus it is possible that influenza A virus infection affects the expression of some other miRNAs not yet covered by the kit used in the current study. Secondly, the virus may interact with miRNA regulatory pathways differently in other cell or tissue types, or in other physiological status. Conclusions In conclusion, based on the broad-catching miRNA microarray approach, we found that dysregulation of miRNA expression is mainly observed in highly pathogenic avian influenza infection.