Unknown

Dataset Information

0

Macrophage-derived exosomes mediate silica-induced pulmonary fibrosis by activating fibroblast in an endoplasmic reticulum stress-dependent manner.


ABSTRACT: Macrophages play a key role in silicosis, and exosomes are potent mediators of intercellular communication. This suggests that macrophage-derived exosomes have a potential contribution to the pathogenesis of silicosis. To investigate whether macrophage-derived exosomes promote or inhibit lung fibrosis, in vitro, silica-exposed macrophage-derived exosomes (SiO2 -Exos) were collected and cocultured with fibroblasts. The expression of collagen I and α-SMA was evaluated. Furthermore, the endoplasmic reticulum (ER) stress markers BIP, XBP1s and P-eIF2α were assessed after treatment with or without the ER stress inhibitor 4-PBA. In vivo, mice were pre-treated with the exosome secretion inhibitor GW4869 prior to silica exposure. After sacrifice, lung tissues were histologically examined, and the expression of proinflammatory cytokines (TNF-α, IL-1β and IL-6) in bronchoalveolar lavage fluid (BALF) was measured. The results showed that the expression of collagen I and α-SMA was up-regulated after treatment with SiO2 -Exos, accompanied by increased expression of BIP, XBP1s and P-eIF2α. Pre-treatment with 4-PBA reversed this effect. More importantly, an in vivo study demonstrated that pre-treatment with GW4869 decreased lung fibrosis and the expression of TNF-α, IL-1β and IL-6 in BALF. These results suggested that SiO2 -Exos are profibrogenic and that the facilitating effect is dependent on ER stress.

SUBMITTER: Qin X 

PROVIDER: S-EPMC8093963 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC7449970 | biostudies-literature
| S-EPMC6929173 | biostudies-literature
| S-EPMC7531166 | biostudies-literature
| S-EPMC5899016 | biostudies-literature
| S-EPMC4001534 | biostudies-other
| S-EPMC4383757 | biostudies-literature
| S-EPMC4071409 | biostudies-literature
| S-EPMC4473261 | biostudies-literature
| S-EPMC5363311 | biostudies-literature
| S-EPMC7863631 | biostudies-literature