Ambient fine particulate matter (PM₂.₅) can change the expression profile of microRNAs (miRs), which may play important roles in mediating inflammatory responses. The present study attempts to investigate the roles of miR-146a-5p in regulating cytokine expression in a human monocytic leukemia cell line (THP-1). Four types of PM₂.₅ extracts obtained from Beijing, China, were subjected to cytotoxic tests in THP-1 cells. These four PM₂.₅ extracts included two water extracts collected from non-heating and heating season (WN and WH), and two organic extracts from non-heating and heating season (DN and DH). Firstly, the four PM₂.₅ extracts caused cytotoxicity, oxidative stress responses, cytokine gene expressions and interleukin 8 (IL-8) release in THP-1 cells, with WH showing the highest cytotoxicity, WN showing the highest oxidative stress and inflammatory responses. Additionally, we observed expression of miR-146a-5p was significantly increased, with the maximal response of six folds in WN group. Cellular autophagy was initiated by PM₂.₅ indicated by related protein and gene expressions. Both RNA interference and autophagy inhibitor were applied to interrupt autophagy process in THP-1 cells. Autophagy dysfunction could alleviate IL-8 expression, suggesting autophagy process regulated cytokine expression and inflammatory response caused by PM₂.₅. A chemical inhibitor was applied to inhibit the function of miR-146a-5p, and then the expressions of IL-8 and autophagic genes were significantly aggravated. Meanwhile, two target genes of miR-146a-5p, interleukin-1 associated-kinase-1 (IRAK1) and tumor-necrosis factor receptor-associated factor-6 (TRAF6) were increased dramatically, which also played important roles in regulation of autophagy. These data suggested miR-146a-5p negatively modulated cytokine expression caused by PM₂.₅ via autophagy process through the target genes of IRAK1 and TRAF6. Our findings raised the concerns of the changes of miR expression profile and following responses caused by PM₂.₅.

We aimed to investigate whether exposure to low-molecular-weight saturated aliphatic aldehydes induces an airway inflammation related to lung toxicity. In previous studies, we identified that several aldehydes induced inflammatory responses through the secretion of pro-inflammatory cytokines.Here, we elucidate on whether hexanal exposure induces the lung inflammatory response through the secretion of cytokines. Hexanal is one of the aldehydes, which are major components of indoor environmental irritants. Based on a multiplexed cytokine antibody array, we investigated the cytokine expression profiles to identify the significant biomarkers of hexanal exposure and to predict the possibility of adverse effects on pulmonary toxicity using in vitro and in vivo model systems. We identified the cytokines as biomarkers involved in LEPTIN, Interleukin(IL)-10, MCP-1, and VEGF that showed similar expression patterns in both in vitro and in vivo models under hexanal exposure. These cytokines are known to be associated with diverse lung diseases, such as lung fibrosis, chronic obstructive pulmonary disease (COPD), and non-small cell lung cancer.Although further studies are needed to identify the mechanisms that underlie hexanal pulmonary toxicity, these results provide the key cytokine biomarkers in response to hexanal exposure and indicate meaningful mechanistic previewing that can be indirectly attributed to lung disease.