Fine particulate matter induces airway inflammation by disturbing the balance between Th1/Th2 and regulation of GATA3 and Runx3 expression in BALB/c mice

摘要

The present study aimed to examine the effects of 2.5 mu m particulate matter (PM2.5) on airway inflammation and to investigate the possible underlying mechanism. Specifically, the focus was on the imbalance of T helper (Th)1/Th2 cells and the dysregulated expression of transcription factors, including trans-acting T cell-specific transcription factor 3 (GATA3), runt-related transcription factor 3 (Runx3) and T-box transcription factor TBX21 (T-bet). In this study, ambient PM2.5 was collected and analyzed, male BALB/c mice were sensitized and treated with PBS, ovalbumin (OVA), PM2.5 or OVA + PM2.5. The effects of PM2.5 alone or + OVA on immunopathological changes, the expression of transcription factors GATA3, Runx3 and T-bet, and the imbalance of Th1/Th2 were investigated. It was found that PM2.5 + OVA co-exposure significantly enhanced inflammatory cell infiltration, increased higher tracheal secretions in lung tissue and upregulated respiratory resistance response to acetylcholine compared with PM2.5 or OVA single exposure and control groups. In addition, higher protein and mRNA expression levels of Th2 inflammatory mediators interleukin (IL)-4, IL-5 and IL-13 in bronchoalveolar lavage fluid were observed in PM2.5 + OVA treated mice, whereas the expression levels of GATA3 and STAT6 were exhibited in mice exposed to OVA + PM2.5 compared with the OVA and PM2.5 groups. By contrast, PM2.5 exposure decreased the protein and mRNA expression levels of Th1 cytokine interferon-gamma and transcription factors Runx3 and T-bet, especially among asthmatic mice, different from OVA group, PM2.5 exposure only failed to influence the expression of T-bet. To conclude, PM2.5 exposure evoked the allergic airway inflammation response, especially in the asthmatic mouse model and led to Th1/Th2 imbalance. These effects worked mainly by upregulating G1TA3 and downregulating Runx3. These data suggested that Runx3 may play an important role in PM2.5-aggravated asthma in BALB/c mice.