scholarly journals Gas6 Ameliorates Inflammatory Response and Apoptosis in Bleomycin-Induced Acute Lung Injury

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1674
Author(s):  
Bo-Min Kim ◽  
Ye-Ji Lee ◽  
Youn-Hee Choi ◽  
Eun-Mi Park ◽  
Jihee Lee Kang
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Apoptotic Cell ◽  
Alveolar Epithelial Cell ◽  
Lung Edema ◽  
Mouse Bone Marrow ◽  
Apoptotic Cell Clearance ◽  
Cell Clearance ◽  
Apoptotic Effects

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-α, interleukin-1β, 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.

scholarly journals A Potential Role for Regulatory T Cells in Apoptotic Cell Clearance by Macrophages in a Murine Model of Acute Lung Injury

2015 ◽  
Vol 29 (S1) ◽  
Author(s):  
Jonathan Proto ◽  
Manikandan Subramanian ◽  
Mohammed Islam ◽  
Jaime Hook ◽  
Galina Gusarova ◽  
...  
Keyword(s):  
T Cells ◽  
Acute Lung Injury ◽  
Regulatory T Cells ◽  
Lung Injury ◽  
Murine Model ◽  
Potential Role ◽  
Apoptotic Cell ◽  
Apoptotic Cell Clearance ◽  
Cell Clearance

Abstract 457: CD36, but not G2A, Modulates Efferocytosis, Inflammation and Fibrosis Following Bleomycin-induced Lung Injury

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Leland L Black ◽  
Brian W Parks ◽  
Kurt A Zimmerman ◽  
Allison E Metz ◽  
Chad Steele ◽  
...  
Keyword(s):  
Lung Injury ◽  
Apoptotic Cell ◽  
Atherosclerotic Lesion ◽  
M2 Macrophage ◽  
Apoptotic Cells ◽  
Alveolar Cells ◽  
Lesion Development ◽  
Apoptotic Cell Clearance ◽  
Arginase 1 ◽  
Cell Clearance

Oxidatively modified lipids and their by-products presented or released by cells undergoing apoptosis are thought to regulate phagocytic uptake of apoptotic cells by macrophages (efferocytosis) through CD36 scavenger and G2A chemotactic receptors. Although the ability of these receptors to mediate clearance of apoptotic cells in the context of atherosclerosis may have significant impact on lesion development and progression/stability, an overabundance of the lipid ligands for these receptors (CD36: oxidized phospholipids, G2A: lysophosphatidylcholine) as a result of oxidative processes associated with atherogenesis could conceivably impair these clearance mechanisms. Because the indolent nature of atherosclerotic lesion development precludes an accurate assessment of the spatial and kinetic features of lesional efferocytosis, we employed a bleomycin-induced model of lung injury to assess the requirement for G2A and CD36 in efferocytosis. This is a model which, similarly to atherogenesis, is associated with oxidative stress, but in which local apoptosis can be induced and efferocytosis subsequently measured over time. As there is substantial in vivo evidence that ApoE has a role in efferocytosis, we included ApoE knock-out mice as controls. Loss of CD36 (similarly to ApoE deficiency) delayed the clearance of apoptotic alveolar cells, potentiated inflammation (increase in lung neutrophils, lung KC [CXCL1] levels, and lung macrophages) and reduced lung fibrosis following bleomycin-induced lung injury. Reduced fibrosis in CD36-/- mice was associated with lower levels of pro-fibrotic TH2 cytokines (IL-9, IL-13, IL-4), decreased expression of the M2 macrophage marker Arginase-1 and reduced interstitial myofibroblasts. Despite the widely held notion that G2A mediates an LPC dependent “find me” signal in macrophages facilitating apoptotic cell clearance, G2A deficiency had no significant effect on the clearance of apoptotic cells in the bleomycin-induced lung injury model. Our results show that CD36 and ApoE (but not G2A) are important for apoptotic cell clearance following lung injury and subsequently modulate inflammatory and fibrotic processes that could impact not only inflammatory lung disease but also atherosclerosis.

scholarly journals TNFα inhibits apoptotic cell clearance in the lung, exacerbating acute inflammation

2009 ◽  
Vol 297 (4) ◽  
pp. L586-L595 ◽  
Author(s):  
Valeria M. Borges ◽  
R. William Vandivier ◽  
Kathleen A. McPhillips ◽  
Jennifer A. Kench ◽  
Konosuke Morimoto ◽  
...  
Keyword(s):  
Lung Injury ◽  
Apoptotic Cell ◽  
Apoptotic Cells ◽  
Neutrophil Accumulation ◽  
Cell Recruitment ◽  
Apoptotic Cell Clearance ◽  
Persistent Inflammation ◽  
Cell Clearance ◽  
Proinflammatory Responses ◽  
Dying Cells

Efficient removal of apoptotic cells is essential for resolution of inflammation. Failure to clear dying cells can exacerbate lung injury and lead to persistent inflammation and autoimmunity. Here we show that TNFα blocks apoptotic cell clearance by alveolar macrophages and leads to proinflammatory responses in the lung. Compared with mice treated with intratracheal TNFα or exogenous apoptotic cells, mice treated with the combination of TNFα plus apoptotic cells demonstrated reduced apoptotic cell clearance from the lungs and increased recruitment of inflammatory leukocytes to the air spaces. Treatment with intratracheal TNFα had no effect on the removal of exogenous apoptotic cells from the lungs of TNFα receptor-1 (p55) and -2 (p75) double mutant mice and no effect on leukocyte recruitment. Bronchoalveolar lavage from mice treated with TNFα plus apoptotic cells contained increased levels of proinflammatory cytokines IL-6, KC, and MCP-1, but exhibited no change in levels of anti-inflammatory cytokines IL-10 and TGF-β. Administration of TNFα plus apoptotic cells during LPS-induced lung injury augmented neutrophil accumulation and proinflammatory cytokine production. These findings suggest that the presence of TNFα in the lung can alter the response of phagocytes to apoptotic cells leading to inflammatory cell recruitment and proinflammatory mediator production.

scholarly journals Long non-coding RNA OIP5-AS1 aggravates acute lung injury by promoting inflammation and cell apoptosis via regulating the miR-26a-5p/TLR4 axis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qingsong Sun ◽  
Man Luo ◽  
Zhiwei Gao ◽  
Xiang Han ◽  
Weiqin Wu ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Cell Apoptosis ◽  
Quantitative Polymerase Chain Reaction ◽  
Luciferase Reporter ◽  
Enzyme Linked Immunosorbent Assay ◽  
Interacting Protein ◽  
Wide Range

Abstract Background Acute lung injury (ALI) is a pulmonary disorder that leads to acute respiration failure and thereby results in a high mortality worldwide. Increasing studies have indicated that toll-like receptor 4 (TLR4) is a promoter in ALI, and we aimed to explore the underlying upstream mechanism of TLR4 in ALI. Methods We used lipopolysaccharide (LPS) to induce an acute inflammatory response in vitro model and a murine mouse model. A wide range of experiments including reverse transcription quantitative polymerase chain reaction, western blot, enzyme linked immunosorbent assay, flow cytometry, hematoxylin–eosin staining, RNA immunoprecipitation, luciferase activity and caspase-3 activity detection assays were conducted to figure out the expression status, specific role and potential upstream mechanism of TLR4 in ALI. Result TLR4 expression was upregulated in ALI mice and LPS-treated primary bronchial/tracheal epithelial cells. Moreover, miR-26a-5p was confirmed to target TLR4 according to results of luciferase reporter assay. In addition, miR-26a-5p overexpression decreased the contents of proinflammatory factors and inhibited cell apoptosis, while upregulation of TLR4 reversed these effects of miR-26a-5p mimics, implying that miR-26a-5p alleviated ALI by regulating TLR4. Afterwards, OPA interacting protein 5 antisense RNA 1 (OIP5-AS1) was identified to bind with miR-26a-5p. Functionally, OIP5-AS1 upregulation promoted the inflammation and miR-26a-5p overexpression counteracted the influence of OIP5-AS1 upregulation on cell inflammatory response and apoptosis. Conclusion OIP5-AS1 promotes ALI by regulating the miR-26a-5p/TLR4 axis in ALI mice and LPS-treated cells, which indicates a promising insight into diagnostics and therapeutics in ALI.

Inhaled nitric oxide reduces lung edema during fluid resuscitation in ovine acute lung injury

2003 ◽  
Vol 29 (10) ◽  
pp. 1790-1797 ◽  
Author(s):  
Henning D. Stubbe ◽  
Martin Westphal ◽  
Hugo Van Aken ◽  
Christoph Hucklenbruch ◽  
Stefan Lauer ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Fluid Resuscitation ◽  
Inhaled Nitric Oxide ◽  
Lung Edema
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