The role of macrophage polarization and related key molecules in pulmonary inflammation and fibrosis induced by coal dust dynamic inhalation exposure in Sprague-Dawley rats.

Coal dust is the main occupational hazard factor during coal mining operations. This study aimed to investigate the role of macrophage polarization and its molecular regulatory network in lung inflammation and fibrosis in Sprague-Dawley rats caused by coal dust exposure. Based on the key exposure parameters (exposure route, dose and duration) of the real working environment of coal miners, the dynamic inhalation exposure method was employed, and a control group and three coal dust groups (4, 10 and 25 mg/m3) were set up. Lung function was measured after 30, 60 and 90 days of coal dust exposure. Meanwhile, the serum, lung tissue and bronchoalveolar lavage fluid were collected after anesthesia for downstream experiments (histopathological analysis, RT-qPCR, ELISA, etc.). The results showed that coal dust exposure caused stunted growth, increased lung organ coefficient and decreased lung function in rats. The expression level of the M1 macrophage marker iNOS was significantly upregulated in the early stage of exposure and was accompanied by higher expression of the inflammatory cytokines TNF-α, IL-1ß, IL-6 and the chemokines IL-8, CCL2 and CCL5, with the most significant trend of CCL5 mRNA in lung tissues. Expression of the M2 macrophage marker Arg1 was significantly upregulated in the mid to late stages of coal dust exposure and was accompanied by higher expression of the anti-inflammatory cytokines IL-10 and TGF-ß. In conclusion, macrophage polarization and its molecular regulatory network (especially CCL5) play an important role in lung inflammation and fibrosis in SD rats exposed to coal dust by dynamic inhalation.

Oxidative stress induced by ultrafine carbon black particles can elicit apoptosis in vivo and vitro.

Although carbon black (CB) particles have potential hazards to human health, the toxicological studies on CB are still limited. The purpose of this study was to investigate the effect of oxidative stress induced by ultrafine CB particles on apoptosis in vivo and vitro. Male C57BL/6 mice were inhalation exposed to CB for 28 days, and 16HBE cells were treated by CB particles and also added antioxidant (NAC). Antioxidant enzymes activities (CAT, SOD, GSH-Px) and ROS in the lungs and cells were evaluated. Apoptosis-related proteins (Bcl-2, Bax, Cleaved Caspase-3, pro-Caspase-3, Caspase-7, Caspase-8, Caspase-9, PARP-1) were tested by Western blot (WB), immunohistochemistry (IHC), and real-time PCR. The reduction of antioxidant enzymes activities and the addition of ROS in CB exposure groups were observed, and the gene and apoptosis-related proteins levels were increased in CB exposure mice. The results of CB-treated 16HBE cells were consistent with those of mice, and apoptosis rate was increased in CB-treated 16HBE cells. When the cells were treated with NAC, ROS induced by CB decreased, SOD and CAT activities of CB-treated 16HBE cells were increased. Apoptosis rate of 16HBE cells treated with NAC and CB was significantly decreased, and the expression of C-Caspase-3 was also decreased. Therefore, oxidative stress induced by ultrafine CB particles can elicit apoptosis in vivo and vitro. Antioxidants can significantly reduce oxidative damage and apoptosis induced by CB.