miR‑206 regulates alveolar type�II epithelial cell Cx43 expression in sepsis‑induced acute lung injury

Objective We investigated the effect of untransplantable bone marrow-derived mesenchymal stem cells (BMSCs) in acute lung injury (ALI) and whether BMSCs attenuate damage of lipopolysaccharide (LPS) to alveolar type II epithelial cells (AECIIs). Methods ALI models were prepared by nebulizing LPS and then BMSCs were infused 1 hour later. We observed histopathological changes of lung tissue and evaluated inflammatory exudation by the wet/dry weight ratio, bronchiolar lavage fluid cell count, and protein concentration determination. Inflammatory and vascular factors were detected by immunohistochemistry and western blotting. For in vitro experiments, AECIIs were stimulated with 10 μg/mL LPS for 4 hours and then BMSCs were seeded in transit inserts to co-culture for 24 hours. The activity of AECIIs was detected. Results In the LPS + BMSCs group, histopathological examination showed that the degree of lung injury was significantly reduced compared with the LPS group. Protein expression of inflammatory and vascular factors was significantly lower with treatment. Optical density values and cell viability of the LPS + BMSCs group were significantly higher than those of the LPS group. Conclusions Untransplanted-BMSCs can inhibit the inflammatory response in ALI and promote repair of AECIIs. This might be due to substances secreted by BMSCs and interaction between these substances.

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Surface expression of CD74 by type II alveolar epithelial cells: a potential mechanism for macrophage migration inhibitory factor-induced epithelial repair

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00525.2007 ◽

2009 ◽

Vol 296 (3) ◽

pp. L442-L452 ◽

Cited By ~ 55

Author(s):

Leigh M. Marsh ◽

Lidija Cakarova ◽

Grazyna Kwapiszewska ◽

Werner von Wulffen ◽

Susanne Herold ◽

...

Keyword(s):

Acute Lung Injury ◽

Epithelial Cell ◽

Epithelial Cells ◽

Lung Injury ◽

Macrophage Migration Inhibitory Factor ◽

Alveolar Epithelial Cells ◽

Macrophage Migration ◽

Type Ii ◽

Alveolar Epithelial ◽

Stimulation Of

Macrophage migration inhibitory factor (MIF) is a pleiotropic proinflammatory cytokine involved in acute lung injury and other processes such as wound repair and tumor growth. MIF exerts pro-proliferative effects on a variety of cell types including monocytes/macrophages, B cells, and gastric epithelial cell lines through binding to the major histocompatibility complex type II-associated invariant chain, CD74. In acute lung injury, inflammatory damage of the alveolar epithelium leads to loss of type I alveolar epithelial cells (AEC-I), which are replaced by proliferation and differentiation of type II alveolar epithelial cells (AEC-II). In this study we have investigated the potential of MIF to contribute to alveolar repair by stimulating alveolar epithelial cell proliferation. We show that murine AEC-II, but not AEC-I, express high surface levels of CD74 in vivo. Culture of AEC-II in vitro resulted in decreased mRNA levels for CD74 and loss of surface CD74 expression, which correlated with a transition of AEC-II to an AEC-I-like phenotype. MIF stimulation of AEC-II induced rapid and prolonged phosphorylation of ERK1/2 and Akt, increased expression of cyclins D1 and E, as well as AEC-II proliferation. Corresponding MIF signaling and enhanced thymidine incorporation was observed after MIF stimulation of MLE-12 cells transfected to overexpress CD74. In contrast, MIF did not induce MAPK activation, gene transcription, or increased proliferation in differentiated AEC-I-like cells that lack CD74. These data suggest a previously unidentified role of MIF-CD74 interaction by inducing proliferation of AEC-II, which may contribute to alveolar repair.

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Alveolar Type II Cells or Mesenchymal Stem Cells: Comparison of Two Different Cell Therapies for the Treatment of Acute Lung Injury in Rats

Cells ◽

10.3390/cells9081816 ◽

2020 ◽

Vol 9 (8) ◽

pp. 1816

Author(s):

Raquel Guillamat-Prats ◽

Marta Camprubí-Rimblas ◽

Ferranda Puig ◽

Raquel Herrero ◽

Neus Tantinyà ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Molecular Mechanisms ◽

Lung Damage ◽

Alveolar Type ◽

Therapeutic Effects ◽

Type Ii Cells ◽

Type Ii ◽

Alveolar Type Ii Cells ◽

Cell Therapies

The use of cell therapies has recently increased for the treatment of pulmonary diseases. Mesenchymal stem/stromal cells (MSCs) and alveolar type II cells (ATII) are the main cell-based therapies used for the treatment of acute respiratory distress syndrome (ARDS). Many pre-clinical studies have shown that both therapies generate positive outcomes; however, the differences in the efficiency of MSCs or ATII for reducing lung damage remains to be studied. We compared the potential of both cell therapies, administering them using the same route and dose and equal time points in a sustained acute lung injury (ALI) model. We found that the MSCs and ATII cells have similar therapeutic effects when we tested them in a hydrochloric acid and lipopolysaccharide (HCl-LPS) two-hit ALI model. Both therapies were able to reduce proinflammatory cytokines, decrease neutrophil infiltration, reduce permeability, and moderate hemorrhage and interstitial edema. Although MSCs and ATII cells have been described as targeting different cellular and molecular mechanisms, our data indicates that both cell therapies are successful for the treatment of ALI, with similar beneficial results. Understanding direct cell crosstalk and the factors released from each cell will open the door to more accurate drugs being able to target specific pathways and offer new curative options for ARDS.

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