Liyun Piao1, Hyun-Jun Park1, Eun-Hye Seo2, Tae-Won Kim3, Je-Kyoun Shin4, Seong-Hyop Kim5. 1. Department of Infection and Immunology, Konkuk University School of Medicine, Seoul, Korea. 2. BK21 Plus, Department of Cellular and Molecular Medicine, Konkuk University School of Medicine, Seoul, Korea. 3. Department of Anesthesiology and Pain Medicine, Konkuk University School of Medicine, Seoul, Korea. 4. Department of Thoracic and Cardiovascular Surgery, Konkuk University School of Medicine, Seoul, Korea. 5. Department of Infection and Immunology, Department of Anesthesiology and Pain Medicine, Department of Medicine, Institute of Biomedical Science and Technology, Konkuk University School of Medicine, Seoul, Korea. yshkim75@daum.net.
Abstract
BACKGROUND: We hypothesized that endoplasmic reticulum stress (ER) would be associated with exosomes in ventilator-induced lung injury (VILI), and that inhibition of ER stress would be linked to less occurrence of VILI or less damage in VILI. METHODS: Mice were randomly allocated to a control group and an Inhibitor group. Normal saline (0.5 mL) was administered intraperitoneally to the control group and 4-phenylbutyric acid (4-PBA) (10 mg/kg mixed in normal saline 0.5 mL) to the inhibitor group. After mechanical ventilation to induce VILI for 2 hours, exosomes from bronchoalveolar lavage (BAL), protein kinase R-like endoplasmic reticulum (PERK), Toll-like receptor 4 (TLR4), and the injury score of the lung tissue were determined. RESULTS: The expression of cluster of differentiation (CD) 63, the marker for exosomes from BAL, was significantly lower (P=0.017) in the inhibitor group [0.967%±0.283% (0.870, 0.810-1.227)] than in the control group [1.559%±0.489% (1.355, 1.259-2.008)]. The expression of PERK and TLR4 from lung tissue was also significantly lower in the inhibitor group than in the control group. The injury score of lung tissue was lower in the inhibitor group than in the control group. CONCLUSIONS: The release of exosomes in mice with VILI was associated with ER stress. The inhibition of ER stress reduced the release of exosomes from the lung with less expression of PERK and TLR4 and reduced pulmonary damage in mice with VILI.
BACKGROUND: We hypothesized that endoplasmic reticulum stress (ER) would be associated with exosomes in ventilator-induced lung injury (VILI), and that inhibition of ER stress would be linked to less occurrence of VILI or less damage in VILI. METHODS:Mice were randomly allocated to a control group and an Inhibitor group. Normal saline (0.5 mL) was administered intraperitoneally to the control group and 4-phenylbutyric acid (4-PBA) (10 mg/kg mixed in normal saline 0.5 mL) to the inhibitor group. After mechanical ventilation to induce VILI for 2 hours, exosomes from bronchoalveolar lavage (BAL), protein kinase R-like endoplasmic reticulum (PERK), Toll-like receptor 4 (TLR4), and the injury score of the lung tissue were determined. RESULTS: The expression of cluster of differentiation (CD) 63, the marker for exosomes from BAL, was significantly lower (P=0.017) in the inhibitor group [0.967%±0.283% (0.870, 0.810-1.227)] than in the control group [1.559%±0.489% (1.355, 1.259-2.008)]. The expression of PERK and TLR4 from lung tissue was also significantly lower in the inhibitor group than in the control group. The injury score of lung tissue was lower in the inhibitor group than in the control group. CONCLUSIONS: The release of exosomes in mice with VILI was associated with ER stress. The inhibition of ER stress reduced the release of exosomes from the lung with less expression of PERK and TLR4 and reduced pulmonary damage in mice with VILI.