New insights into the treatment mechanisms of Vitamin D on PM2.5-induced toxicity and inflammation in mouse renal tubular epithelial cells.

BACKGROUND

Particulate matter (PM2.5) could induce renal injury other than lung and heart damage. The renal injury always displays in the way of renal inflammation. Vitamin D (VitD) has been identified as renal-protective factor with its anti-inflammatory effect.

AIM OF THE STUDY: This study explored the therapeutic effect of VitD receptor (VDR) agonist (paricalcitol) on PM2.5-induced toxicity and inflammation in mouse renal tubular epithelial cells (mRTECs) and its molecular mechanisms.

METHODS

The variation between PM2.5 and paricalcitol solution was investigated in different concentration solutions with transmission electron microscopy (TEM), laser-induced fluorescence (LIF) and liquid chromatography-mass spectrometry (LC-MS). The detoxication and anti-inflammation effects of paricalcitol on PM2.5 in vitro were analyzed by LIF, MTT, western blot (WB), ELISA and flow cytometry (FCM).

RESULTS AND

CONCLUSION

PM2.5 became more compact after paricalcitol treatment on account of stripped polycyclic aromatic hydrocarbons (PAHs). In the cellular experiments, PM2.5 (160 μg/ml) evoked mRTECs inflammation and apoptosis through the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) /IL-1β axis, while paricalcitol (120 μg/ml) reversed these processes. The fluorescence intensity of cell supernatant detected by PAH-LIF was weakened after adding paricalcitol, compared with.PM2.5 treatment alone. Interestingly, paricalcitol can significantly reduce the concentration of highly toxic PAHs and increase the proportion of nontoxic small PAHs. Furthermore, VDR expression was negatively correlated with the inflammation and cell apoptosis. In summary, VitD and VDR promote biological detoxication on PM2.5 though PAH degradation from a molecular effect, and exert anti-inflammatory effects against NLRP3/IL-1β axis caused by PM2.5.