Serum‐derived exosomes from SD rats induce inflammation in macrophages through the mTOR pathway

Abstract

Inhalation of beryllium and its compounds can cause lung injuries, resulting from inflammation and oxidative stress. Multivesicular bodies (MVB), such as exosomes, are membrane vesicles produced by early and late endosomes that mediate intercellular communications. However, the role of exosomes in beryllium toxicity has not been elucidated. This current study aimed to investigate the functional role of exosomes in lung injury resulting from beryllium sulfate (BeSO 4 ). Here, Sprague-Dawley (SD) rats were exposed to 4, 8, and 12 mg/kg BeSO 4 by nonexposed intratracheal instillation. Murine macrophage (RAW 264.7) cells were pretreated with 50 nmol/L rapamycin (an mTOR signaling pathway inhibitor) for 30 min and then cultured for 24 h with 100 μg/mL exosomes, which had been previously isolated from the serum of 12 mg/kg BeSO 4 -treated SD rats. Compared with those of the controls, exposure to BeSO 4 in vivo increased LDH activity, elevated levels of inflammatory cytokines (IL-10, TNF-α, and IFN-γ) alongside inflammation-related proteins expression (COX-2 and iNOS), and enhanced secretion of exosomes from the SD rat's serum. Moreover, the BeSO 4 -Exos-induced upregulation of LDH activity and inflammatory responses in RAW 264.7 cells can be alleviated following pretreatment with rapamycin. Collectively, these results suggest that serum exosomes play an important role in pulmonary inflammation induced by BeSO 4 in RAW 264.7 cells via the mTOR pathway.

Human serum‐derived exosomes modulate macrophage inflammation to promote VCAM1‐mediated angiogenesis and bone regeneration

“…24 While another study showed that rat-derived serum-Exo inhibits macrophage inflammation. 25 This study found that serum-Exo from healthy donors was efficiently internalized by macrophages. Newly formed blood vessels play an important role in bone regeneration via osteogenesis-angiogenesis coupling.…”

“… 24 While another study showed that rat‐derived serum‐Exo inhibits macrophage inflammation. 25 This study found that serum‐Exo from healthy donors was efficiently internalized by macrophages. Moreover, serum‐Exo treatment alleviated LPS‐induced macrophage inflammation in vitro.…”

“…Lu et al showed that serum‐Exo from tumour patients promotes macrophage inflammation 24 . While another study showed that rat‐derived serum‐Exo inhibits macrophage inflammation 25 . This study found that serum‐Exo from healthy donors was efficiently internalized by macrophages.…”