Cordyceps Militaris Alleviates Severity of Murine Acute Lung Injury Through miRNAs-Mediated CXCR2 Inhibition

Background: Acute lung injury (ALI) is characterized by rapid induction of inflammation at the alveolar-capillary membrane, and immunosuppressive mechanisms were shown to contribute to its resolution. Despite the central role of lymphocytes in initiating and mediating an inflammatory response, their influx dynamics in ALI has not been examined. Methods: We collected mini-BAL samples from the lung of ALI patients over a maximum period of 7 days, and examined the lymphocyte composition. Results: CD3⁺CD4⁺IFN-gamma⁺ Th1 cells were detected early on in all patients examined, while IL-10-producing B cells and CD3⁺CD4⁺CD25^hiFoxp3⁺ Treg cells appeared later. Interestingly, IL-10-producing B cells appeared earlier than Tregs in most subjects, which possibly exerted anti-inflammatory function before Tregs. We then found that in patients with earlier recruitment of IL-10-producing B cells, the magnitude of Th1 inflammation decreased significantly over time, which was not observed in patients with later recruitment of IL-10-producing B cells. Furthermore, early IL-10-producing B cell recruiters also had significantly earlier recruitment of Tregs and better survival than late IL-10-producing B cell recruiters. Conclusion: This study provided data on the alveolar infiltration of lymphocytes during ALI, which suggested an inhibitory role of IL-10-producing B cells in ALI and emphasized the importance of controlling inflammation during the initial stage of ALI.

“…1C) [24,25]. We did not find that these B cells were particularly high in terms of CD24 or CD38 expression, common markers of regulatory B cells in autoimmune diseases [26].…”

Section: Cd19contrasting

confidence: 57%

Early Recruitment of IL-10-Producing B Cells Into Alveoli Improved the Resolution of Acute Lung Injury

Xu¹,

Xu²,

Li³

et al. 2016

“…The activity of myeloperoxidase (MPO), a lung injury marker, can be used to evaluate the accumulation of neutrophils in the lungs [36]. Serum chemokines, such as MIG (CXCL9), MIP-2 (CXCL2) and RANTES (CCL5), are related to lung injury [37-40]. LPS is generally used to induce ALI in mice.…”

Section: Discussionmentioning

confidence: 99%

Fibrocytes Ameliorate Acute Lung Injury by Decreasing Inflammatory Cytokine and Chemokine Levels and Reducing Neutrophil Accumulation in the Lung

Tai

Ding

et al. 2017

Background/Aims: Acute lung injury (ALI) remains a severe disease that threatens human life around the world. To decrease the mortality of ALI and improve ALI treatment efficacy, the development of more ALI treatments is urgently needed. Whether fibrocytes directly participate in ALI has not been studied. Therefore, a mouse model of ALI was induced with lipopolysaccharide (LPS). Methods: Fibrocytes were harvested from peripheral blood mononuclear cells of bleomycin mice and identified by using flow cytometry to detect the expression of molecular makers. The fibrocytes were injected for the treatment of acute lung injury mice. The curative effects were evaluated by using ELISA to determine the cytokines (including TNF-α, IL-6 and IFN-γ) concentrations in bronchoalveolar lavage fluid (BALF) supernatant. Results: The concentrations of cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interferon-γ (IFN-γ) were increased in mice with ALI induced with LPS. The concentrations of TNF-α, IL-6, and IFN-γ as well as their mRNA and protein expression levels were decreased by administration of fibrocytes. The effect of fibrocytes in ameliorating ALI was time dependent. LPS treatment induced an increase in myeloperoxidase (MPO) activity, whereas the fibrocyte treatment caused inhibition of MPO activity as well as expression of the neutrophil-chemoattractant chemokine macrophage inflammatory protein 2 (MIP-2). Conclusion: Taken together, these data suggest that fibrocytes ameliorated ALI by suppressing inflammatory cytokines and chemokines as well as by decreasing the accumulation of neutrophils in the lung.

“…The cellular pathology of ALI includes breakdown of alveolar-capillary membrane integrity, excessive neutrophil migration and production and secretion of pro-inflammatory cytokines, e.g. CXCL1, CXCL2, interleukin (IL)-6 and tumor necrosis factor (TNF)-α [5][6][7]. Injuries occur to both pulmonary endothelial cells (PECs) and alveolar epithelial cells after ALI, in which the recovery of the disease could also result in loss of parts of the lung function [1][2][3][4].…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal Stem Cells Alleviate LPS-Induced Acute Lung Injury in Mice by MiR-142a-5p-Controlled Pulmonary Endothelial Cell Autophagy

Zi-chao

You

2016

Background/Aims: Damages of pulmonary endothelial cells (PECs) represent a critical pathological process during acute lung injury (ALI), and precede pulmonary epithelial cell injury, and long-term lung dysfunction. Transplantation of mesenchymal stem cells (MSCs) has proven therapeutic effects on ALI, whereas the underlying mechanisms remain ill-defined. Method: We transplanted MSCs in mice and then induced ALI using Lipopolysaccharides (LPS). We analyzed the changes in permeability index and lung histology. Mouse PECs were isolated by flow cytometry based on CD31 expression and then analyzed for autophagy-associated factors LC3 and Beclin-1 by Western blot. Beclin-1 mRNA was determined by RT-qPCR. In vitro, we performed bioinformatics analyses to identify the MSCs-regulated miRNAs that target Beclin-1, and confirmed that the binding was functional by 3'-UTR luciferase reporter assay. Results: We found that MSCs transplantation significantly reduced the severity of LPS-induced ALI in mice. MSCs increased autophagy of PECs to promote PEC survival. MSCs increased Beclin-1 protein but not mRNA. MiR-142a-5p was found to target the 3'-UTR of Beclin-1 mRNA to inhibit its protein translation in PECs. MSCs reduced the levels of miR-142a-5p in PECs from LPS-treated mice. Conclusion: MSCs may alleviate LPS-ALI through downregulation of miR-142a-5p, which allows PECs to increase Beclin-1-mediated cell autophagy.