GRP78 and CHOP modulate macrophage apoptosis and the development of bleomycin-induced pulmonary fibrosis

• DOI: 10.1002/path.4738
• Publication Date: 2016-05-02T16:25:04Z
• Authors: Ehab A Ayaub; Philipp S Kolb; Zahraa Mohammed-Ali; Victor Tat; James Murphy; Pierre-Simon Bellaye; Chiko Shimbori; Felix J Boivin; Rocky Lai; Edward G Lynn; Šárka Lhoták; Darren Bridgewater; Martin RJ Kolb; Mark D Inman; Jeffrey G Dickhout; Richard C Austin; Kjetil Ask
• Keywords: Mice, Knockout; 0301 basic medicine; Caspase 3; Pulmonary Fibrosis; Apoptosis; Endoplasmic Reticulum Stress; 3. Good health; Bleomycin; Mice; 03 medical and health sciences; Macrophages, Alveolar; Unfolded Protein Response; Animals; Endoplasmic Reticulum Chaperone BiP; Heat-Shock Proteins; Transcription Factor CHOP

Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) have been associated with fibrotic lung disease, although exactly how they modulate this process remains unclear. Here we investigated role of GRP78, main UPR regulator, in an experimental model injury fibrosis. Grp78(+/-) , Chop(-/-) wild type C57BL6/J mice were exposed to bleomycin by oropharyngeal intubation lungs examined at days 7 21. We demonstrate here that strongly protected from bleomycin-induced fibrosis, as shown immunohistochemical analysis, collagen content function measurements. In inflammatory phase model, a reduced number macrophages increased TUNEL-positive cells observed mice. Dual situ hybridization experiments showed macrophage population was also positive for cleaved caspase-3 Chop mRNA, respectively. contrast, administration resulted quasi-static elastance extracellular matrix deposition parenchymal arginase-1-positive negative caspase-3. The data presented indicate is activated tissue localized macrophages. GRP78- CHOP-mediated apoptosis found protect against Overall, dependent on GRP78-mediated events provides evidence polarization may play process. Copyright © 2016 Pathological Society Great Britain Ireland. Published John Wiley & Sons, Ltd.