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The Role of Endoplasmic Reticulum Stress in Silica-Induced Apoptosis in Alveolar Macrophages
Occupational and Environmental Lung Diseases SESSION TITLE: Occupational and Environmental Lung Diseases SESSION TYPE: Original Investigation Poster PRESENTED ON: Saturday, April 16, 2016 at 11:45 AM - 12:45 PM
The Role of Endoplasmic Reticulum Stress in Silica-Induced Apoptosis in Alveolar Macrophages
PURPOSE: To explore the role of Endoplasmic Reticulum Stress (ERS) and its mediated apoptosis in Alveolar Macrophages (AM) induced by silica. METHODS: RAW264.7 cells were incubated with 200mg/ml silica for indicated times (0, 6, 12, 24, 48h). The morphological changes of cells were observed by transmission electron microscopy (TEM). Real-time PCR and Western blot were performed to detect the protein expression of BiP and CHOP. DAPI staining, Flow Cytometry (FCM) and Cleaved caspase-3 were used to measure apoptosis. In the prevention experiments, the ERS inhibitor 4-PBA was used to inhibit ERS and evaluate the changes of cell apoptosis. RESULTS: Under silica treatment, RAW264.7 cells showed irregular shapes, mitochondria swelling, ER lumen enlarged. We also found that silica induction increased levels of ER stress indicators BiP and CHOP in a time-dependent manner. Moreover, silica treatment could induce cell apoptosis in a time-dependent manner. Given different concentrated 4-PBA, we could found the expression of BiP and CHOP decreased in a dose-dependent. Furthermore, 4-PBA could inhibit silica-induced apoptosis in macrophages. CONCLUSIONS: These findings indicate that Silica induces ER Stress and apoptosis in alveolar macrophages, and the apoptosis is dependent on ER stress. CLINICAL IMPLICATIONS: This study provides the first demonstration that ERS plays an important role in silica-induced apoptosis in alveolar macrophages. These findings offer new and important clues regarding molecular mechanisms involved in silica-induced apoptosis and provide insights for understanding and possible prevention of silica induced fibrosis. DISCLOSURE: The following authors have nothing to disclose: Yongbin Hu, Xia Wu, Pinhua Pan No Product/Research Disclosure Information DOI:
http://dx.doi.org/10.1016/j.chest.2016.02.431
Copyright ª 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.
journal.publications.chestnet.org
415A
OCCUPATIONAL AND ENVIRONMENTAL LUNG DISEASES
Yongbin Hu PhD* Xia Wu MA; and Pinhua Pan PhD Department of Pathology, Xiangya Hospital, Central South University, Changsha, China
The Role of Endoplasmic Reticulum Stress in Silica-Induced Apoptosis in Alveolar Macrophages
PURPOSE: To explore the role of Endoplasmic Reticulum Stress (ERS) and its mediated apoptosis in Alveolar Macrophages (AM) induced by silica. METHODS: RAW264.7 cells were incubated with 200mg/ml silica for indicated times (0, 6, 12, 24, 48h). The morphological changes of cells were observed by transmission electron microscopy (TEM). Real-time PCR and Western blot were performed to detect the protein expression of BiP and CHOP. DAPI staining, Flow Cytometry (FCM) and Cleaved caspase-3 were used to measure apoptosis. In the prevention experiments, the ERS inhibitor 4-PBA was used to inhibit ERS and evaluate the changes of cell apoptosis. RESULTS: Under silica treatment, RAW264.7 cells showed irregular shapes, mitochondria swelling, ER lumen enlarged. We also found that silica induction increased levels of ER stress indicators BiP and CHOP in a time-dependent manner. Moreover, silica treatment could induce cell apoptosis in a time-dependent manner. Given different concentrated 4-PBA, we could found the expression of BiP and CHOP decreased in a dose-dependent. Furthermore, 4-PBA could inhibit silica-induced apoptosis in macrophages. CONCLUSIONS: These findings indicate that Silica induces ER Stress and apoptosis in alveolar macrophages, and the apoptosis is dependent on ER stress. CLINICAL IMPLICATIONS: This study provides the first demonstration that ERS plays an important role in silica-induced apoptosis in alveolar macrophages. These findings offer new and important clues regarding molecular mechanisms involved in silica-induced apoptosis and provide insights for understanding and possible prevention of silica induced fibrosis. DISCLOSURE: The following authors have nothing to disclose: Yongbin Hu, Xia Wu, Pinhua Pan No Product/Research Disclosure Information DOI:
http://dx.doi.org/10.1016/j.chest.2016.02.431
Copyright ª 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.
journal.publications.chestnet.org
415A
OCCUPATIONAL AND ENVIRONMENTAL LUNG DISEASES
Yongbin Hu PhD* Xia Wu MA; and Pinhua Pan PhD Department of Pathology, Xiangya Hospital, Central South University, Changsha, China