Gas6 Ameliorates Inflammatory Response and Apoptosis in Bleomycin-Induced Acute Lung Injury
- 주제(키워드) Gas6 , bleomycin , inflammation , apoptosis , efferocytosis
- 주제(기타) Biochemistry & Molecular Biology
- 주제(기타) Medicine, Research & Experimental
- 주제(기타) Pharmacology & Pharmacy
- 설명문(일반) [Kim, Bo-Min; Lee, Ye-Ji; Choi, Youn-Hee; Kang, Jihee Lee] Ewha Womans Univ, Coll Med, Dept Physiol, Seoul 07804, South Korea; [Kim, Bo-Min; Lee, Ye-Ji; Choi, Youn-Hee; Kang, Jihee Lee] Ewha Womans Univ, Coll Med, Inflammat Canc Microenvironm Res Ctr, Seoul 07804, South Korea; [Park, Eun-Mi] Ewha Womans Univ, Coll Med, Dept Pharmacol, Seoul 07804, South Korea
- 등재 SCIE, SCOPUS
- OA유형 gold, Green Published
- 발행기관 MDPI
- 발행년도 2021
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000190764
- 본문언어 영어
- Published As https://doi.org/10.3390/biomedicines9111674
- PubMed https://pubmed.ncbi.nlm.nih.gov/34829903
초록/요약
Acute lung injury (ALI) is characterized by alveolar damage, lung edema, and exacerbated inflammatory response. Growth arrest-specific protein 6 (Gas6) mediates many different functions, including cell survival, proliferation, inflammatory signaling, and apoptotic cell clearance (efferocytosis). The role of Gas6 in bleomycin (BLM)-induced ALI is unknown. We investigated whether exogenous administration of mouse recombinant Gas6 (rGas6) has anti-inflammatory and anti-apoptotic effects on BLM-induced ALI. Compared to mice treated with only BLM, the administration of rGas6 reduced the secretion of proinflammatory cytokines, including tumor necrosis factor-alpha, interleukin-1 beta, and macrophage inflammatory protein-2, and increased the secretion of hepatocyte growth factor in bronchoalveolar lavage (BAL) fluid. rGas6 administration also reduced BLM-induced inflammation and apoptosis as evidenced by reduced neutrophil recruitment into the lungs, total protein levels in BAL fluid, caspase-3 activity, and TUNEL-positive lung cells in lung tissue. Apoptotic cell clearance by alveolar macrophages was also enhanced in mice treated with both BLM and rGas6 compared with mice treated with only BLM. rGas6 also had pro-resolving and anti-apoptotic effects in mouse bone marrow-derived macrophages and alveolar epithelial cell lines stimulated with BLM in vitro. These findings indicate that rGas6 may play a protective role in BLM-induced ALI.
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